BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-codin...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-coding RNA semaphorin 6Aantisense RNA 1(SEMA6A-AS1)was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.AIM To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.METHODS The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction,immunohistochemistry and Western blot.A growth curve,colony formation,wound-healing and transwell(with or without Matrigel)assays were respectively performed to assess the proliferation,migration and invasion abilities of HCC cells.Cell cycle and apoptosis assays were performed by flow cytometry.To investigate the potential mechanism underpinning SEMA6A-AS1,we utilized tagged RNA affinity purification,dual luciferase reporter assay and immunofluorescence.RESULTS Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression.SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level,high Edmondson-Steiner grade and poor prognosis.SEMA6A-AS1 significantly inhibited the proliferation,migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation.SEMA6A protein promoted the proliferation,migration and invasion of HCC cells by regulating the actin cytoskeleton.CONCLUSION Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation.SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.展开更多
The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understoo...The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.展开更多
The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research...The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.展开更多
The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,N...The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,No.6,2018,pp.869–878.展开更多
The published article titled“Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression inNon-Small Cell Lung Cancer”has been retracted fromOncology Research,Vol.25,No.6,2017,pp.1027–1037.DOI...The published article titled“Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression inNon-Small Cell Lung Cancer”has been retracted fromOncology Research,Vol.25,No.6,2017,pp.1027–1037.DOI:10.3727/096504016X14822800040451 URL:https://www.techscience.com/or/v25n6/56885 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.展开更多
BACKGROUND Colorectal cancer(CRC)is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals.Chemotherapy,a crucial adjuvant systemic therapy for CRC management,often leads ...BACKGROUND Colorectal cancer(CRC)is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals.Chemotherapy,a crucial adjuvant systemic therapy for CRC management,often leads to resistance through poorly characterized underlying molecular mechanisms.The long noncoding RNA SNHG5 is highly expressed in CRC and promotes tumor proliferation and invasion,prompting us to hypothesize that SNHG5 may play a crucial role in the chemotherapeutic agent 5-fluorouracil(5-Fu)resistance in CRC.AIM To identify the function and mechanism of SNHG5 in 5-Fu resistance in CRC.METHODS Quantitative real-time polymerase chain reaction was performed to examine the expression of SNHG5 in CRC tissues from 225-Fu-sensitive patients and 145-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells.Cell viability and apoptosis were assessed in SNHG5-overexpressing CRC cells and SNHG5-knockdown 5-Furesistant CRC cells.SNHG5 function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model.SNHG5 interactions with microRNAs were predicted by bioinformatics analysis.Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between SNHG5 and miR-26b.Rescue experiments were performed to validate the functional interaction between SNHG5 and the miR-26b/p-glycoprotein(Pgp)axis.RESULTS SNHG5 expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells.In vitro functional experiments demonstrated that SNHG5 overexpression significantly reduced cell apoptosis and enhanced cell viability,whereas SNHG5 knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment.In a xenograft mouse model,we confirmed that SNHG5 overexpression led to a reduction in 5-Fu sensitivity in CRC in vivo.Mechanistically,SNHG5 acted as a molecular sponge for miR-26b.Rescue experiments validated that SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.CONCLUSION SNHG5/miR-26b/Pgp regulates CRC chemosensitivity,providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.展开更多
The published article titled“Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis”has been retracted from Oncology ...The published article titled“Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis”has been retracted from Oncology Research,Vol.28,No.1,2020,pp.65-73.展开更多
Long non-coding RNAs(lncRNAs)play pivotal roles in the regulation of gene expression,particularly in maintaining pluripotency and directing stem cell.By orchestrating stem cell fate decisions and lineage commitment th...Long non-coding RNAs(lncRNAs)play pivotal roles in the regulation of gene expression,particularly in maintaining pluripotency and directing stem cell.By orchestrating stem cell fate decisions and lineage commitment through epigenetic,transcriptional,and post-transcriptional mechanisms,lncRNAs have emerged as key modulators in developmental biology.Their therapeutic potential has garnered increasing interest,especially in the contexts of regenerative medicine,disease modeling,targeted delivery systems,and precision therapeutics.This review presents a comprehensive overview of the mechanisms by which lncRNAs govern stem cell differentiation and examines emerging lncRNA-based therapeutic strategies,emphasizing major challenges and prospective research directions in this rapidly advancing field.展开更多
BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become anoth...BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.展开更多
BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary...BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.展开更多
BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify geno...BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.展开更多
BACKGROUND Gastric cancer,characterized by a multifactorial etiology and high heterogeneity,continues to confound researchers in terms of its pathogenesis.Curcumin,a natural anticancer agent,exhibits therapeutic promi...BACKGROUND Gastric cancer,characterized by a multifactorial etiology and high heterogeneity,continues to confound researchers in terms of its pathogenesis.Curcumin,a natural anticancer agent,exhibits therapeutic promise in gastric cancer.Its effects include promoting cell apoptosis,curtailing tumor angiogenesis,and enhancing sensitivity to radiation and chemotherapy.Long noncoding RNAs(lncRNAs)have garnered significant attention as biomarkers for early screening,diagnosis,treatment,and drug response because of their remarkable specificity and sensitivity.Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis,clinical staging,metastasis,drug sensitivity,and prognosis in gastric cancer.A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer develop-ment can provide novel insights for precision treatment and tailored management of patients with gastric cancer.This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregu-lating specific lncRNAs and modulating gastric cancer onset and progression.AIM To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis,proliferation,and invasion.Furthermore,these findings were validated in clinical samples.METHODS The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation,flow cytometry to investigate its effects on apoptosis,and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells.Western blotting was used to gauge changes in the protein expression levels of CDK6,CDK4,Bax,Bcl-2,caspase-3,P65,and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment.Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction(qRT-PCR)in BGC-823 and MGC-803 cells.AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis,proliferation,migration,and invasion of gastric cancer cells.Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways.RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics.RESULTS Curcumin induced apoptosis and hindered proliferation,migration,and invasion of gastric cancer cells in a dose-and time-dependent manner.LncRNA AC022424.2 was upregulated after curcumin treatment,and its knockdown enhanced cancer cell aggressiveness.LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways.LncRNA AC022424.2 downregulation was correlated with lymph node metastasis,making it a potential diagnostic and prognostic marker.CONCLUSION Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2.This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation.The results of this study enhance our understanding of gastric cancer development and precision treatment.展开更多
The incidence rates of hepatocellular carcinoma(HCC)have increased in recent decades.Despite advancements in therapy and early diagnosis improving shortterm prognosis,long-term outcomes remain poor.Long noncoding RNAs...The incidence rates of hepatocellular carcinoma(HCC)have increased in recent decades.Despite advancements in therapy and early diagnosis improving shortterm prognosis,long-term outcomes remain poor.Long noncoding RNAs(lncRNAs)and lipid metabolism play crucial roles in the development and progression of HCC.Enhanced lipid synthesis promotes HCC progression,and lncRNAs can reprogram the expression of lipogenic enzymes.Consequently,lipid metabolism-related(LMR)-lncRNAs regulate lipid anabolism,accelerating the onset and progression of HCC.This suggests that LMR-lncRNAs could serve as novel prognostic biomarkers and therapeutic targets.展开更多
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivo...This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a malignancy found globally.Accumulating studies have shown that long noncoding RNAs(lncRNAs)play critical roles in HCC.However,the function of lncRNA in HCC remains poorly u...BACKGROUND Hepatocellular carcinoma(HCC)is a malignancy found globally.Accumulating studies have shown that long noncoding RNAs(lncRNAs)play critical roles in HCC.However,the function of lncRNA in HCC remains poorly understood.AIM To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms.METHODS We measured the expression of lncRNA W42 in HCC tissues and cells(Huh7 and SMMC-7721)by quantitative reverse transcriptase polymerase chain reaction.Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression.HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42.Cell functions were detected by cell counting Kit-8(CCK-8),colony formation,flow cytometry and Transwell assays.The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays.An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo.The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC.RESULTS In this study,we identified a novel lncRNA(lncRNA W42),and investigated its biological functions and clinical significance in HCC.LncRNA W42 expression was upregulated in HCC tissues and cells.Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC,and inhibited cell apoptosis.LncRNA W42 directly bound to DBN1 and activated the downstream pathway.LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo.The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times.CONCLUSION In vitro and in vivo results suggested that the novel lncRNA W42,which is upregulated in HCC,may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.展开更多
Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are noncodingRNAs (ncRNAs) that occupy over 90% of the human genome, and their mainfunction is to directly or indirectly regulate messenger RNA (mRNA) expressionand...Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are noncodingRNAs (ncRNAs) that occupy over 90% of the human genome, and their mainfunction is to directly or indirectly regulate messenger RNA (mRNA) expressionand participate in the tumorigenesis and progression of malignances. Inparticular, some lncRNAs can interact with miRNAs as competing endogenousRNAs (ceRNAs) to modulate mRNA expression. Accordingly, these RNAmolecules are interrelated and coordinate to form a dynamic lncRNA-mediatedceRNA regulatory network. Mounting evidence has revealed that lncRNAs thatact as ceRNAs are closely related to tumorigenesis. To date, numerous studieshave established many different regulatory networks in hepatocellular carcinoma(HCC), and perturbations in these ceRNA interactions may result in the initiationand progression of HCC. Herein, we emphasize recent advances concerning thebiological function of lncRNAs as ceRNAs in HCC, with the aim of elucidating themolecular mechanism underlying these HCC-related RNA molecules andproviding novel insights into the diagnosis and treatment of HCC.展开更多
Increasing numbers of long noncoding RNAs(lncRNAs)are implicated in breast cancer oncogenicity.However,the contribution of LINC02568 toward breast cancer progression remains unclear and requires further investigation....Increasing numbers of long noncoding RNAs(lncRNAs)are implicated in breast cancer oncogenicity.However,the contribution of LINC02568 toward breast cancer progression remains unclear and requires further investigation.Herein,we evaluated LINC02568 expression in breast cancer and clarified its effect on disease malignancy.We also investigated the mechanisms underlying the pro-oncogenic role of LINC02568.Consequently,LINC02568 was upregulated in breast cancer samples,with a notable association with worse overall survival.Functionally,depleted LINC02568 suppressed cell proliferation,colony formation,and metastasis,whereas LINC02568 overexpression exerted the opposite effects.Our mechanistic investigations suggested that LINC02568 was physically bound to and sequestered microRNA-874-3p(miR-874-3p).Furthermore,miR-874-3p mediated suppressive effects in breast cancer cells by targeting cyclin E1(CCNE1).LINC02568 positively controlled CCNE1 expression by sequestering miR-874-3p.Rescue experiments revealed that increased miR-874-3p or decreased CCNE1 expression recovered cell growth and motility functions induced by LINC02568 in breast cancer cells.In conclusion,the tumor-promoting functions of LINC02568 in breast cancer cells were enhanced by sequestering miR-874-3p and consequently over-expressing CCNE1.Our data may facilitate the identification of novel therapeutic targets in clinical settings.展开更多
Many studies have illustrated the significance of long noncoding RNAs in oncogenesis and promotion of breast cancer(BC).However,the biological roles of CCDC183 antisense RNA 1(CCDC183-AS1)in BC have rarely been charac...Many studies have illustrated the significance of long noncoding RNAs in oncogenesis and promotion of breast cancer(BC).However,the biological roles of CCDC183 antisense RNA 1(CCDC183-AS1)in BC have rarely been characterized.Thus,we explored whether CCDC183-AS1 is involved in the malignancy of BC and elucidated the possible underlying mechanisms.Our data confirmed elevated CCDC183-AS1 expression in BC,which was associated with poor clinical outcomes.Functionally,knocking down CCDC183-AS1 hampered cell proliferation,colony formation,migration,and invasion in BC.Additionally,the absence of CCDC183-AS1 restrained tumor growth in vivo.Mechanistically,CCDC183-AS1 executed as a competitive endogenous RNA in BC cells by decoying microRNA-3918(miR-3918)and consequently overexpressing fibroblast growth factor receptor 1(FGFR1).Furthermore,functional rescue experiments confirmed that inactivation of the miR-3918/FGFR1 regulatory axis by inhibiting miR-3918 or increasing FGFR1 expression could abrogate the CCDC183-AS1 ablation-mediated repressive effects in BC cells.In summary,CCDC183-AS1 deteriorates the malignancy of BC cells by controlling miR-3918/FGFR1 regulatory axis.We believe that our study can deepen our understanding of BC etiology and contribute to an improvement in treatment choices.展开更多
OBJECTIVE: To profile the liver cancer specific long noncoding RNAs(lnc RNAs) and competing endogenous RNA(ce RNA) networks of Hepatitis B virus(HBV)-associated hepatocarcinogensis(HCG) and to examine the effect of co...OBJECTIVE: To profile the liver cancer specific long noncoding RNAs(lnc RNAs) and competing endogenous RNA(ce RNA) networks of Hepatitis B virus(HBV)-associated hepatocarcinogensis(HCG) and to examine the effect of compound K on the expression of identified ce RNA networks.METHODS: Based on lnc RNA and messenger RNA(m RNA) microarray data of HBV-associated liver cancer, the current study profiles the cancer specific lnc RNAs and ce RNA networks of HBV-associated HCG through comprehensive application of Reg RNA 2, mi RTar Base and Pearson correlation coefficient analysis. Compound K-treated liver cancer cells were harvested for analysis of transcriptional levels of both enoyl-Co A hydratase and 3-hydroxyacyl Co A dehydrogenase(EHHADH)-AS1 and ENTPD5.RESULTS: The results revealed that 11 Encyclopedia of DNA Elements annotated lnc RNAs were differentially expressed in the process of HBV-associated HCG. Among these lnc RNAs, 95 potential ce RNA networks with highly positively correlated expression profiles between the interacting lnc RNAs and m RNAs(Pearson correlation coefficient ≥ 0.7) were constructed. Of note, two HBV-associated ce RNA networks, EHHADH-AS1-hsa-mi R-4459-ectonucleoside triphosphate diphosphohydrolase 5 and LINC01018-hsa-mi RNA-574-5p-glucose-6-phosphatase catalytic subunit, with Pearson correlation coefficient ≥ 0.9, may play a critical role in hepatocellular carcinoma development, which was supported by experimental evidence. Interestingly, compound K, an intestinal bacterial metabolite of ginseng protopanaxadiol saponin, which has been proven to promote apoptosis of human hepatocellular carcinoma cells, was found to impede the down-regulation of EHHADH-AS1 in several liver cancer cell lines including Hep G3 B, Huh-7 and plc/prf/5 cells.CONCLUSION: Comprehensive application of co-expression network analysis and prediction of RNA interaction may be a feasible strategy to unravel the potential ce RNA networks involved in the process of human diseases.展开更多
基金Supported by Natural Science Foundation of Hunan Province,No.2021JJ41048 and No.S2019JJQNJJ2012and Changsha Natural Science Foundation,No.kq2208400.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-coding RNA semaphorin 6Aantisense RNA 1(SEMA6A-AS1)was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.AIM To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.METHODS The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction,immunohistochemistry and Western blot.A growth curve,colony formation,wound-healing and transwell(with or without Matrigel)assays were respectively performed to assess the proliferation,migration and invasion abilities of HCC cells.Cell cycle and apoptosis assays were performed by flow cytometry.To investigate the potential mechanism underpinning SEMA6A-AS1,we utilized tagged RNA affinity purification,dual luciferase reporter assay and immunofluorescence.RESULTS Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression.SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level,high Edmondson-Steiner grade and poor prognosis.SEMA6A-AS1 significantly inhibited the proliferation,migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation.SEMA6A protein promoted the proliferation,migration and invasion of HCC cells by regulating the actin cytoskeleton.CONCLUSION Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation.SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.
基金supported by the National Key Research and Development Program(2022YFA1104401)Beijing Municipal Government grant(Beijing Laboratory of Oral Health,PXM2021-014226-000041)+3 种基金Beijing Municipal Govemment(Beijing Scholar Program,PXM2021-014226-000020)National Natural Science Foundation of China(82030031,92149301,81991504,L2224038,82270945)Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202201)Chinese Research Unit of Tooth Development and Regeneration,Academy of Medical Sciences(2019-12M-5-031).
文摘The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs(lncRNAs).However,the dynamics of lncRNA expression during human tooth development remain poorly understood.In this research,we examined the lncRNAs present in the dental epithelium(DE)and dental mesenchyme(DM)at the late bud,cap,and early bell stages of human fetal tooth development through bulk RNA sequencing.Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis.Specific lncRNAs expressed in the DE and DM,such as PANCR,MIR205HG,DLX6-AS1,and DNM3OS,were identified through a combination of bulk RNA sequencing and single-cell analysis.Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ,such as the inner enamel epithelium and coronal dental papilla(CDP).Functionally,we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells.These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
文摘The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.
文摘The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,No.6,2018,pp.869–878.
文摘The published article titled“Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression inNon-Small Cell Lung Cancer”has been retracted fromOncology Research,Vol.25,No.6,2017,pp.1027–1037.DOI:10.3727/096504016X14822800040451 URL:https://www.techscience.com/or/v25n6/56885 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.
基金Supported by the National Natural Science Foundation of China,No.82404088China Postdoctoral Science Foundation,No.2023M730587Changshu Talent Scientific Project,No.KCH202304.
文摘BACKGROUND Colorectal cancer(CRC)is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals.Chemotherapy,a crucial adjuvant systemic therapy for CRC management,often leads to resistance through poorly characterized underlying molecular mechanisms.The long noncoding RNA SNHG5 is highly expressed in CRC and promotes tumor proliferation and invasion,prompting us to hypothesize that SNHG5 may play a crucial role in the chemotherapeutic agent 5-fluorouracil(5-Fu)resistance in CRC.AIM To identify the function and mechanism of SNHG5 in 5-Fu resistance in CRC.METHODS Quantitative real-time polymerase chain reaction was performed to examine the expression of SNHG5 in CRC tissues from 225-Fu-sensitive patients and 145-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells.Cell viability and apoptosis were assessed in SNHG5-overexpressing CRC cells and SNHG5-knockdown 5-Furesistant CRC cells.SNHG5 function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model.SNHG5 interactions with microRNAs were predicted by bioinformatics analysis.Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between SNHG5 and miR-26b.Rescue experiments were performed to validate the functional interaction between SNHG5 and the miR-26b/p-glycoprotein(Pgp)axis.RESULTS SNHG5 expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells.In vitro functional experiments demonstrated that SNHG5 overexpression significantly reduced cell apoptosis and enhanced cell viability,whereas SNHG5 knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment.In a xenograft mouse model,we confirmed that SNHG5 overexpression led to a reduction in 5-Fu sensitivity in CRC in vivo.Mechanistically,SNHG5 acted as a molecular sponge for miR-26b.Rescue experiments validated that SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.CONCLUSION SNHG5/miR-26b/Pgp regulates CRC chemosensitivity,providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.
文摘The published article titled“Overexpression of the Long Noncoding RNA FOXD2-AS1 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma Through the miR-195/Akt/mTOR Axis”has been retracted from Oncology Research,Vol.28,No.1,2020,pp.65-73.
基金Supported by the National Natural Science Foundation of China,No.32200755 and No.32200621the Natural Science Foundation of Gansu Province,No.23JRRA696。
文摘Long non-coding RNAs(lncRNAs)play pivotal roles in the regulation of gene expression,particularly in maintaining pluripotency and directing stem cell.By orchestrating stem cell fate decisions and lineage commitment through epigenetic,transcriptional,and post-transcriptional mechanisms,lncRNAs have emerged as key modulators in developmental biology.Their therapeutic potential has garnered increasing interest,especially in the contexts of regenerative medicine,disease modeling,targeted delivery systems,and precision therapeutics.This review presents a comprehensive overview of the mechanisms by which lncRNAs govern stem cell differentiation and examines emerging lncRNA-based therapeutic strategies,emphasizing major challenges and prospective research directions in this rapidly advancing field.
基金Supported by the Natural Science Funds for Young Scholar of Hebei,China,No.H2020206108the Subject of Health Commission of Hebei,China,No.20210151.
文摘BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.
基金Supported by Innovative Team of Jiangsu Province,No.CXTDA2017042Jiangsu Provincial Medical Youth Talent,No.QNRC2016508In-Hospital Project of Taizhou People's Hospital,No.ZL201930.
文摘BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.
文摘BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.
基金Supported by the Natural Science Foundation of Gansu Province,China,No.20JR5RA356 and No.22JR5RA511the Lanzhou City Chengguan District Science and Technology Planning Project,No.2016-7-17.
文摘BACKGROUND Gastric cancer,characterized by a multifactorial etiology and high heterogeneity,continues to confound researchers in terms of its pathogenesis.Curcumin,a natural anticancer agent,exhibits therapeutic promise in gastric cancer.Its effects include promoting cell apoptosis,curtailing tumor angiogenesis,and enhancing sensitivity to radiation and chemotherapy.Long noncoding RNAs(lncRNAs)have garnered significant attention as biomarkers for early screening,diagnosis,treatment,and drug response because of their remarkable specificity and sensitivity.Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis,clinical staging,metastasis,drug sensitivity,and prognosis in gastric cancer.A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer develop-ment can provide novel insights for precision treatment and tailored management of patients with gastric cancer.This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregu-lating specific lncRNAs and modulating gastric cancer onset and progression.AIM To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis,proliferation,and invasion.Furthermore,these findings were validated in clinical samples.METHODS The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation,flow cytometry to investigate its effects on apoptosis,and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells.Western blotting was used to gauge changes in the protein expression levels of CDK6,CDK4,Bax,Bcl-2,caspase-3,P65,and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment.Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction(qRT-PCR)in BGC-823 and MGC-803 cells.AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis,proliferation,migration,and invasion of gastric cancer cells.Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways.RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics.RESULTS Curcumin induced apoptosis and hindered proliferation,migration,and invasion of gastric cancer cells in a dose-and time-dependent manner.LncRNA AC022424.2 was upregulated after curcumin treatment,and its knockdown enhanced cancer cell aggressiveness.LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways.LncRNA AC022424.2 downregulation was correlated with lymph node metastasis,making it a potential diagnostic and prognostic marker.CONCLUSION Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2.This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation.The results of this study enhance our understanding of gastric cancer development and precision treatment.
基金Supported by National Natural Science Foundation of China,No.82170593,No.81700503the National Key Research and Development Program of China,No.2021YFC2700802.
文摘The incidence rates of hepatocellular carcinoma(HCC)have increased in recent decades.Despite advancements in therapy and early diagnosis improving shortterm prognosis,long-term outcomes remain poor.Long noncoding RNAs(lncRNAs)and lipid metabolism play crucial roles in the development and progression of HCC.Enhanced lipid synthesis promotes HCC progression,and lncRNAs can reprogram the expression of lipogenic enzymes.Consequently,lipid metabolism-related(LMR)-lncRNAs regulate lipid anabolism,accelerating the onset and progression of HCC.This suggests that LMR-lncRNAs could serve as novel prognostic biomarkers and therapeutic targets.
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
文摘This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a malignancy found globally.Accumulating studies have shown that long noncoding RNAs(lncRNAs)play critical roles in HCC.However,the function of lncRNA in HCC remains poorly understood.AIM To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms.METHODS We measured the expression of lncRNA W42 in HCC tissues and cells(Huh7 and SMMC-7721)by quantitative reverse transcriptase polymerase chain reaction.Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression.HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42.Cell functions were detected by cell counting Kit-8(CCK-8),colony formation,flow cytometry and Transwell assays.The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays.An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo.The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC.RESULTS In this study,we identified a novel lncRNA(lncRNA W42),and investigated its biological functions and clinical significance in HCC.LncRNA W42 expression was upregulated in HCC tissues and cells.Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC,and inhibited cell apoptosis.LncRNA W42 directly bound to DBN1 and activated the downstream pathway.LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo.The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times.CONCLUSION In vitro and in vivo results suggested that the novel lncRNA W42,which is upregulated in HCC,may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.
文摘Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are noncodingRNAs (ncRNAs) that occupy over 90% of the human genome, and their mainfunction is to directly or indirectly regulate messenger RNA (mRNA) expressionand participate in the tumorigenesis and progression of malignances. Inparticular, some lncRNAs can interact with miRNAs as competing endogenousRNAs (ceRNAs) to modulate mRNA expression. Accordingly, these RNAmolecules are interrelated and coordinate to form a dynamic lncRNA-mediatedceRNA regulatory network. Mounting evidence has revealed that lncRNAs thatact as ceRNAs are closely related to tumorigenesis. To date, numerous studieshave established many different regulatory networks in hepatocellular carcinoma(HCC), and perturbations in these ceRNA interactions may result in the initiationand progression of HCC. Herein, we emphasize recent advances concerning thebiological function of lncRNAs as ceRNAs in HCC, with the aim of elucidating themolecular mechanism underlying these HCC-related RNA molecules andproviding novel insights into the diagnosis and treatment of HCC.
文摘Increasing numbers of long noncoding RNAs(lncRNAs)are implicated in breast cancer oncogenicity.However,the contribution of LINC02568 toward breast cancer progression remains unclear and requires further investigation.Herein,we evaluated LINC02568 expression in breast cancer and clarified its effect on disease malignancy.We also investigated the mechanisms underlying the pro-oncogenic role of LINC02568.Consequently,LINC02568 was upregulated in breast cancer samples,with a notable association with worse overall survival.Functionally,depleted LINC02568 suppressed cell proliferation,colony formation,and metastasis,whereas LINC02568 overexpression exerted the opposite effects.Our mechanistic investigations suggested that LINC02568 was physically bound to and sequestered microRNA-874-3p(miR-874-3p).Furthermore,miR-874-3p mediated suppressive effects in breast cancer cells by targeting cyclin E1(CCNE1).LINC02568 positively controlled CCNE1 expression by sequestering miR-874-3p.Rescue experiments revealed that increased miR-874-3p or decreased CCNE1 expression recovered cell growth and motility functions induced by LINC02568 in breast cancer cells.In conclusion,the tumor-promoting functions of LINC02568 in breast cancer cells were enhanced by sequestering miR-874-3p and consequently over-expressing CCNE1.Our data may facilitate the identification of novel therapeutic targets in clinical settings.
文摘Many studies have illustrated the significance of long noncoding RNAs in oncogenesis and promotion of breast cancer(BC).However,the biological roles of CCDC183 antisense RNA 1(CCDC183-AS1)in BC have rarely been characterized.Thus,we explored whether CCDC183-AS1 is involved in the malignancy of BC and elucidated the possible underlying mechanisms.Our data confirmed elevated CCDC183-AS1 expression in BC,which was associated with poor clinical outcomes.Functionally,knocking down CCDC183-AS1 hampered cell proliferation,colony formation,migration,and invasion in BC.Additionally,the absence of CCDC183-AS1 restrained tumor growth in vivo.Mechanistically,CCDC183-AS1 executed as a competitive endogenous RNA in BC cells by decoying microRNA-3918(miR-3918)and consequently overexpressing fibroblast growth factor receptor 1(FGFR1).Furthermore,functional rescue experiments confirmed that inactivation of the miR-3918/FGFR1 regulatory axis by inhibiting miR-3918 or increasing FGFR1 expression could abrogate the CCDC183-AS1 ablation-mediated repressive effects in BC cells.In summary,CCDC183-AS1 deteriorates the malignancy of BC cells by controlling miR-3918/FGFR1 regulatory axis.We believe that our study can deepen our understanding of BC etiology and contribute to an improvement in treatment choices.
基金Supported by the Natural Science Foundation of China:The roles and mechanisms of RXRαin HBx-induced DNMT3a up-regulation in hepatocellular carcinoma(No.81372272)The role of Foxo1-m TOR signal axis in regulating bioenergetic metabolism transition during NK Cell activation(No.81520108029)
文摘OBJECTIVE: To profile the liver cancer specific long noncoding RNAs(lnc RNAs) and competing endogenous RNA(ce RNA) networks of Hepatitis B virus(HBV)-associated hepatocarcinogensis(HCG) and to examine the effect of compound K on the expression of identified ce RNA networks.METHODS: Based on lnc RNA and messenger RNA(m RNA) microarray data of HBV-associated liver cancer, the current study profiles the cancer specific lnc RNAs and ce RNA networks of HBV-associated HCG through comprehensive application of Reg RNA 2, mi RTar Base and Pearson correlation coefficient analysis. Compound K-treated liver cancer cells were harvested for analysis of transcriptional levels of both enoyl-Co A hydratase and 3-hydroxyacyl Co A dehydrogenase(EHHADH)-AS1 and ENTPD5.RESULTS: The results revealed that 11 Encyclopedia of DNA Elements annotated lnc RNAs were differentially expressed in the process of HBV-associated HCG. Among these lnc RNAs, 95 potential ce RNA networks with highly positively correlated expression profiles between the interacting lnc RNAs and m RNAs(Pearson correlation coefficient ≥ 0.7) were constructed. Of note, two HBV-associated ce RNA networks, EHHADH-AS1-hsa-mi R-4459-ectonucleoside triphosphate diphosphohydrolase 5 and LINC01018-hsa-mi RNA-574-5p-glucose-6-phosphatase catalytic subunit, with Pearson correlation coefficient ≥ 0.9, may play a critical role in hepatocellular carcinoma development, which was supported by experimental evidence. Interestingly, compound K, an intestinal bacterial metabolite of ginseng protopanaxadiol saponin, which has been proven to promote apoptosis of human hepatocellular carcinoma cells, was found to impede the down-regulation of EHHADH-AS1 in several liver cancer cell lines including Hep G3 B, Huh-7 and plc/prf/5 cells.CONCLUSION: Comprehensive application of co-expression network analysis and prediction of RNA interaction may be a feasible strategy to unravel the potential ce RNA networks involved in the process of human diseases.
