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 ...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
In the article“Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene”(Oncology Research.2024,Vol.32,No.7,pp.1185–1195.doi:10....In the article“Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene”(Oncology Research.2024,Vol.32,No.7,pp.1185–1195.doi:10.32604/or.2023.030771,https://www.techscience.com/or/v32n7/57163),an inadvertent error occurred during the compilation of Fig.3H.This needed corrections to ensure the accuracy and integrity of the data presented.展开更多
Objective:To investigate the effects of arecoline on HPV-positive cervical cells and unveil its underlying mechanism in cervical carcinogenesis.Methods:The cytotoxicity of arecoline was determined and the effect of su...Objective:To investigate the effects of arecoline on HPV-positive cervical cells and unveil its underlying mechanism in cervical carcinogenesis.Methods:The cytotoxicity of arecoline was determined and the effect of subtoxic concentrations of arecoline on the expression of viral oncoproteins and transcriptional factors was examined in CaSki and SiHa cells.HPV16 promoter activity was evaluated in a plasmid containing HPV16 long control region(pGL3-HPV16LCR)-transfected cells.Cell proliferation,cell migration,and number of colonies were assessed by MTT,wound healing assay,and colony-forming assay,respectively.Results:Arecoline at 0.01μg/mL significantly upregulated HPV16 E6 and E7 oncoproteins in both CaSki and SiHa cells.It also upregulated the expression level of c-Fos and c-Jun mRNAs,and c-Myc protein in CaSki and SiHa cells.In addition,arecoline at subtoxic concentrations(0.0025 and 0.01μg/mL)significantly induced HPV16 promoter activity in pGL3-16LCR-transfected cells.It also promoted SiHa and CaSki cell proliferation,migration,and colony formation.Conclusions:Arecoline at subtoxic concentrations promotes the proliferation,migration,and colony formation of CaSki and SiHa cells via upregulation of c-Fos,c-Jun,c-Myc,and HPV16 E6 and E7 expressions.展开更多
BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has sho...BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.展开更多
BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically conside...BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.展开更多
Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet...Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.展开更多
There was no detectable expression of c-fos,but a little c-myc,high c-fms and mederate high IGF-ⅡmRNA in the untreated human hepatocarcinoma cell SMMC- 7721.After treatment with 10 μmol/L retinoic acid or 0.5 mmol/L...There was no detectable expression of c-fos,but a little c-myc,high c-fms and mederate high IGF-ⅡmRNA in the untreated human hepatocarcinoma cell SMMC- 7721.After treatment with 10 μmol/L retinoic acid or 0.5 mmol/L dibutyryl cyclic-3',5'adenosine monophosphate(db-cAMP),the c-fos was transiently expressed within 20- 60mins.If the treatment of RA or db-cAMP prolonged to 1-5 days, the transcriptions of c- myc were increased,reaching the highest level on the 2nd and 4th day.Simultaneously the transcriptions of c- fms and IGF- Ⅱwere gradually decreased.On the 5th day of the treatment,c-fms and IGF-ⅡmRNA were decreased to 32% and 14%respectively of the control (untreated cell) value by RA,and 35% and 22%respectively by db-cAMP.The biological significance of the above mentioned results was discussed.展开更多
Expression of oncogene and anti-oncogene products in 12 cases of male breast carcinoma was studied.Positive staining was seen in 6 cases for c-myc,6 cases for EGFR.4 cases for c-erbB-2 cases for N-ras,5 cases for Rb a...Expression of oncogene and anti-oncogene products in 12 cases of male breast carcinoma was studied.Positive staining was seen in 6 cases for c-myc,6 cases for EGFR.4 cases for c-erbB-2 cases for N-ras,5 cases for Rb and 3 cases for P53.One case was positive and 4 cases were negative for all above mentioned oncogene and antioncogene products.In addition,Cathepsin D(Cath-D),ER.PR,AR.PCNA and AgNOR were also assayed.In all the cases showed c-erbB-2 or P53 positive were Cath-D positive.The significance of expression of c-erbB-2,c-myc,Cath-D,ER and PR in male breast carcinoma was emphatically discussed.展开更多
Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instea...Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instead integrate their genetic material into the host genome thus,affecting cell cycle and tumor suppression.This deregulation also leads to impaired immune function and promotes tumor progression by disrupting the removal of infected cells.Generally,innate immunity consists of two important members,including mitochondria and cell deaths,which impact each other as well.Due to the close correlation between viruses,cell death pathways(apoptosis,necroptosis,and pyroptosis),and mitochondria(mitochondrial antiviral-signaling protein and reactive oxygen species generation),targeting these immune system representatives may offer therapeutic strategies to control the progression of oncogenic viral infections.Some previous studies have covered the association of oncogenic viruses with mitochondria and cell death pathways,respectively,but mitochondria and cell death interact with each other,separately,and this interaction may play a role in the progression of cancer induced by oncogenic viruses.Hence,the purpose of this review is to discuss the relationship between cell death,mitochondria,and viral oncogenesis,focusing on the most surveyed oncogenic viruses’mechanisms of action.展开更多
Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal ma-lignancies with limited treatment efficacy.Advances in precision oncology,enabled by next-generation sequencing,have highlighted key molecular ta...Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal ma-lignancies with limited treatment efficacy.Advances in precision oncology,enabled by next-generation sequencing,have highlighted key molecular targets.Kirsten rat sarcoma viral oncogene homolog mutations,present in up to 90%of cases,drive aggressive biology,though most variants remain undruggable;allele-specific inhibitors and exosome-based RNA interference are under exploration.Breast cancer susceptibility gene 1/2 mutations occur in 4%-7%of patients,con-ferring sensitivity to platinum agents and poly(ADP-ribose)polymerase inhi-bitors.Other rare but actionable alterations-such as v-raf murine sarcoma viral oncogene homolog B1(V600),neurotrophic tyrosine receptor kinase,fibroblast growth factor receptor 2,and RET fusions-show benefit in tumor-agnostic trials,broadening options for selected subgroups.Immunotherapy is limited,as high tumor mutational burden and mismatch repair deficiency are uncommon in PDAC,though predictive when present.Co-mutations in tumor protein p53,cyclin-dependent kinase inhibitor 2A,and SMAD4 further stratify prognosis and influence therapy response.Cross-cancer analyses underscore the necessity of PDAC-specific strategies despite shared genomic drivers.Collectively,these insights support routine germline and somatic testing,enrollment in biomarker-matched trials,and rational combination strategies,establishing molecular profiling as central to advancing precision treatment in pancreatic cancer.展开更多
This editorial comments on the review by Da Silva et al,published in the World Journal of Clinical Oncology which focuses on the molecular perspectives of lung cancer.With the rapid development of molecular technology...This editorial comments on the review by Da Silva et al,published in the World Journal of Clinical Oncology which focuses on the molecular perspectives of lung cancer.With the rapid development of molecular technology,new diagnostic methods are constantly emerging,including liquid biopsy,the identification of gene mutations,and the monitoring biomarkers,thus providing precise in-formation with which to identify the occurrence and development of lung cancer.Biomarkers,such as circulating tumor cells,circulating tumor DNA,and cir-culating RNA can provide helpful information for clinical application.Common types of genetic mutations and immune checkpoints include epidermal growth factor receptor,anaplastic lymphoma kinase,c-ROS proto-oncogene 1,progra-mmed death-1 and cytotoxic T-lymphocyte-associated protein.According to specific biomarkers,targeted therapy and immunotherapy can improve survival outcomes based on the types of gene mutation and immune checkpoints.The application of molecular approaches can facilitate our ability to control the progression of disease and select appropriate therapeutic strategies for patients with lung cancer.展开更多
Objective To evaluate the expression pattern of non-SMC condensin II complex subunit D3(NCAPD3)in hepatocellular carcinoma(HCC)tissues,assess its association with clinical characteristics,and explore the effects of NC...Objective To evaluate the expression pattern of non-SMC condensin II complex subunit D3(NCAPD3)in hepatocellular carcinoma(HCC)tissues,assess its association with clinical characteristics,and explore the effects of NCAPD3 on HCC cells and the potential underlying mechanisms.Methods NCAPD3 expression in HCC tumors and adjacent noncancerous tissues was quantified via quantitative PCR.Patients were divided into high-and low-expression groups on the basis of NCAPD3 levels,and associations with clinical parameters were assessed.The effects of NCAPD3 knockdown and the phosphatidylinositol-3-kinase(PI3K)agonist Y-P 740 on cell functions were examined via cell proliferation,Transwell migration,and invasion assays.Differentially expressed genes following NCAPD3 knockdown in SMMC-7721 cells were identified via mRNA sequencing.Western blotting was performed to measure NCAPD3,AKT serine/threonine kinase 1(AKT1),and phosphorylated AKT1 levels.Results NCAPD3 mRNA expression was notably upregulated in HCC tissues as compared with that in adjacent noncancer tissues.A positive correlation was observed between NCAPD3 expression and both lymphatic and distant metastases in patients with HCC.NCAPD3 knockdown reduced the proliferation and metastasis of SMMC-7721 and Huh-7 cells.mRNA sequencing revealed 140 downregulated genes and 125 upregulated genes.Further validation experiments confirmed that NCAPD3 modulated the PI3K-AKT signalling pathway and that the PI3K agonist Y-P 740 counteracted the effects of NCAPD3 knockdown.Conclusions Elevated NCAPD3 expression was strongly correlated with HCC metastasis.NCAPD3 inhibition impedes HCC cell growth and metastatic potential by suppressing the PI3K–AKT signalling pathway.展开更多
The heat sensitivity of Human gingival squamous carcinoma Ca9-22 cells with oncogene erbB-1/EGFR and Chinese hamster V79 cells of normal thermosensitivity as control was investigated.Colony forming ability of the trea...The heat sensitivity of Human gingival squamous carcinoma Ca9-22 cells with oncogene erbB-1/EGFR and Chinese hamster V79 cells of normal thermosensitivity as control was investigated.Colony forming ability of the treated cells was assayed in vitro. Heat-treatment period-survival and the concerned curves were drawn.The slopes of exponentially regressing parts of the survival curves were estimated in the TO values of cellular thermosensitivity and subjected to Arrhenius analysis-The 42-44℃ time-survival curves of Ca9-22 cells showed biphasic slopes which indicated the presence of thermotolerance induction during continuous heating even at 44℃ while for the V79 cells the biphasic slopes due to thermotolerance induction were shown in temperatures at and before 42℃. In comparison of TO values with V79 cells, those of Ca9-22 cells were longer (less thermosensitive) by about 2.1 fold at 43℃ and 1-2 fold at 44℃. Both V79 and Ca9-22 cells were sensitized by 44--42℃ step-down heating (SDH).42℃ beat treatment period-survival curves of 44℃ ( 5minute) preheated V79 cells; while Ca9-22 cells under the same treatment condition for not only 5 minutes but 20 minutes showed biphasic slope, which indicated the Presence of thermotolerance. The thermosensitization ratio (TSR) of Ca9-22 cells were smaller than V79 cells.Arrhenius curves a breaking points at 44℃ and 43℃ for Ca9-22 and V79 cells, respectively. The activation energies of V79 cells were 145kcallmole and 400kcal/mole above and below 43℃ (p < 0.05), respectively,while those of Ca9-22 cells were 200 kcal/mole and 250kcal/mole above and below 44℃ (P <0.05), respectively.These data suggested that oncogene erbB-1 /EGFRcontained in Ca9-22 cells may contribute to reducethermosensitivity and variety in term of G￣1 phase as shown in fractionated Hydroxyurea treatment.展开更多
Lipid metabolism plays a pivotal role in gastric cancer(GC)progression,characterized by complex metabolic reprogramming that supports tumor growth and survival.This narrative review comprehensively examines the dysreg...Lipid metabolism plays a pivotal role in gastric cancer(GC)progression,characterized by complex metabolic reprogramming that supports tumor growth and survival.This narrative review comprehensively examines the dysregulation of lipid metabolism-associated genes,including fatty acid synthase(FASN),ATPcitrate lyase,acetyl-CoA carboxylases,FA binding proteins,sterol regulatory element-binding proteins,and other key enzymes.These genes facilitate critical oncogenic processes by enhancing FA synthesis,modifying cellular signaling,and supporting cancer cell proliferation,migration,and therapy resistance.Metabolic adaptations observed in GC include increased de novo lipogenesis,altered enzymatic activities,and modified protein lipidation,which contribute to tumor aggressiveness.The review highlights the potential of targeting these metabolic pathways as a therapeutic strategy,demonstrating how inhibiting specific enzymes like FASN,ATP-citrate lyase,and stearoyl-CoA desaturase 1 can induce apoptosis,disrupt cancer stem cell properties,and potentially overcome treatment resistance.By elucidating the intricate interactions between lipid metabolism genes and cancer progression,this review provides insights into novel diagnostic and therapeutic approaches for managing GC.展开更多
AIM To study the significance of C-erbB-2 oncogene amplification in gastric cancer.METHODS C-erbB-2 oncogene amplification was examined by using differential polymerase chain reaction (dPCR) in surgical and endoscopic...AIM To study the significance of C-erbB-2 oncogene amplification in gastric cancer.METHODS C-erbB-2 oncogene amplification was examined by using differential polymerase chain reaction (dPCR) in surgical and endoscopic specimens of 83 cases of gastric cancer and 101 metastatic lymph nodes.RESULTS C-erbB-2 amplification was found in 28.9% (24/ 83) surgical specimens and 20.5% (17/ 83) endoscopic ones of gastric cancer patients. The amplification was significant in both types of specimens of advanced cancer cases (P＜0.05) and surgical specimens with lymph node metastasis (P＜0.01). The incidence of C-erbB-2 amplification in lymph nodes with metastasis was higher than in primary sites (surgical specimens, P＜0.05). The patients with amplification tumors had poorer 5-year survival rates than those with unamplification ones in the early cancers and well to moderately differentiated adenocarcinomas (P＜0.05). The same surgical samples were tested again by Southern blot hybridization to ascertain C-erbB-2 amplification, and the positive rate of C-erbB-2 amplification (15.7%) was lower than that of dPCR (28.9%, P＜0.05).CONCLUSION Examining C-erbB-2 amplification by dPCR is a quick, simple, reliable and independent method, and is helpful in predicting prognosis and metastatic potential of gastric cancer.展开更多
AIM: To observe the protein and mRNA expression of bcl-2 oncogene in gastric precancerous lesions (GPL) and to analyze its correlation with syndromes in traditional Chinese medicine (TCM). METHODS: Sixty-seven patient...AIM: To observe the protein and mRNA expression of bcl-2 oncogene in gastric precancerous lesions (GPL) and to analyze its correlation with syndromes in traditional Chinese medicine (TCM). METHODS: Sixty-seven patients with GPL confirmed by gastroscopy and pathology were studied,including 39 cases of moderate gastric mucosal dysplasia,19 cases of severe gastric mucosa dysplasia, 9 cases of incomplete colon metaplasia. In syndrome differentiation of TCM,17 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by qi stagnation, 21 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by stomach heat, 29 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by blood stasis. Protein and mRNA expression of bcl-2 oncogene were detected by labeled streptavidin biotin (LSAB) immunohist-ochemistry and in situ hybridization respectively. RESULTS: Abnormal expression of protein and mRNA on bcl-2 oncogene was found in GPL,which increased gradually with the course of lesions. In moderate and severe gastric mucosal dysplasia and incomplete colon metaplasia,there was no difference in the expression of bcl-2 oncogene (P>0.05).In different accompanying syndromes, the expression of protein and mRNA on bcl-2 oncogene increased gradually in the following order: deficiency of both qi and yin of the spleen and stomach accompanying qi stagnation→stomach heat→blood stasis. In GPL, compared with accompanying blood stasis, there was an obvious difference in the expression of bcl-2 oncogene between the syndrome of qi and yin deficiency of the spleen and stomach and accompanying stomach heat, so did accompanying qi stagnation (the level of protein: X2=8.45, P<0.05;the level of mRNA: X2=7.35, P<0.05). CONCLUSION: Apoptosis-associated bcl-2 oncogene is abnormally expressed in GPL,which correlates with different accompanying syndromes in TCM.展开更多
Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the ...Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of CSCC.The difference was statistically significant(X^2=7.26.P=0.001<0.05).While expression of c-fos protein was positively related to differentiation of CSCC.which was statistically significant(X^2=7.47,P=0.0012<0.025).Conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of CSCC differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.展开更多
Sustained expression of the Spi-1/PU.1 and Fli-1 oncoproteins blocks globin gene activation in mouse erythroleukemia cells; however, only Spi-1/PU.1 expression inhibits the inclusion of exon 16 in the mature 4.1R mRNA...Sustained expression of the Spi-1/PU.1 and Fli-1 oncoproteins blocks globin gene activation in mouse erythroleukemia cells; however, only Spi-1/PU.1 expression inhibits the inclusion of exon 16 in the mature 4.1R mRNA. This splicing event is crucial for a functional 4.1R protein and, therefore, for red blood cell membrane integrity. This report demonstrates that Spi-1/PU.1 downregulation induces the activation of TRIM10/hematopoietic RING finger 1 （HERF1）, a member of the tripartite motif （TRIM）/RBCC protein family needed for globin gene transcription. Additionally, we demonstrate that TRIM10/HERF1 is required for the regulated splicing of exon 16 during late erythroid differentia- tion. Using inducible overexpression and silencing approaches, we found that： （1） TRIM10/HERF1 knockdown inhibits hemoglobin production and exon splicing and triggers cell apoptosis in dimethylsulfoxide （DMSO）-induced cells; （2） TRIM10/HERF1 upregulation is required but is insufficient on its own to activate exon retention; （3） Fli-1 has no effect on TRIM10/HERFI expression, whereas either DMSO-induced downregulation or shRNA-knockdown of Spi-I/PU.I expression is sufficient to activate TRIM10/HERF1 expression; and （4） Spi-1/PU.1 knockdown triggers both the transcription and the splicing events independently of the chemical induction. Altogether, these data indicate that primary Spi-1/PU.1 downregulation acts on late erythroid differentiation through at least two pathways, one of which requires TRIM10/HERF1 upregulation and parallels the Spi-1/PU.1-induced Fli-1 shutoff regulatory cascade.展开更多
BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in...BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.展开更多
Objective: To explore the expression of c-Met mRNA in nasopharyngeal carcinomas (NPC) and its relation with clinical biological behavior. Methods: In situ hybridisation was used to detect mRNA expression of c-Met in 1...Objective: To explore the expression of c-Met mRNA in nasopharyngeal carcinomas (NPC) and its relation with clinical biological behavior. Methods: In situ hybridisation was used to detect mRNA expression of c-Met in 15 cases of non-tumor nasopharyngeal (NP), 55 cases of NPC. Results: The positive rates of c-Met mRNA in NP and NPC cells were 13.3% (2/15) and 61.8% (34/55) respectively. The expression of c-Met mRNA was significantly correlated with lymph node metastasis, local invasion (skull base erosion), and clinical stage. In cases with cervical lymph node metastasis, local invasion, and clinical stage III and IV (UICC), the positive rates of expression of c-Met mRNA were significantly higher than that in those without the conditions mentioned above (P < 0.05 or P < 0.01). But it was not significantly correlated with age, gender, histo- logic grade, and cranial nerve palsy (P > 0.05). Conclusion: The abnormal expression of c-Met gene was well correlated with the biological behavior of metastasis and invasion. To detection the expression of c-Met mRNA could serve as an important index to estimate the prognosis of NPC. C-Met may be a new diagnostic/therapeutic target of NPC.展开更多
文摘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.
文摘In the article“Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene”(Oncology Research.2024,Vol.32,No.7,pp.1185–1195.doi:10.32604/or.2023.030771,https://www.techscience.com/or/v32n7/57163),an inadvertent error occurred during the compilation of Fig.3H.This needed corrections to ensure the accuracy and integrity of the data presented.
文摘Objective:To investigate the effects of arecoline on HPV-positive cervical cells and unveil its underlying mechanism in cervical carcinogenesis.Methods:The cytotoxicity of arecoline was determined and the effect of subtoxic concentrations of arecoline on the expression of viral oncoproteins and transcriptional factors was examined in CaSki and SiHa cells.HPV16 promoter activity was evaluated in a plasmid containing HPV16 long control region(pGL3-HPV16LCR)-transfected cells.Cell proliferation,cell migration,and number of colonies were assessed by MTT,wound healing assay,and colony-forming assay,respectively.Results:Arecoline at 0.01μg/mL significantly upregulated HPV16 E6 and E7 oncoproteins in both CaSki and SiHa cells.It also upregulated the expression level of c-Fos and c-Jun mRNAs,and c-Myc protein in CaSki and SiHa cells.In addition,arecoline at subtoxic concentrations(0.0025 and 0.01μg/mL)significantly induced HPV16 promoter activity in pGL3-16LCR-transfected cells.It also promoted SiHa and CaSki cell proliferation,migration,and colony formation.Conclusions:Arecoline at subtoxic concentrations promotes the proliferation,migration,and colony formation of CaSki and SiHa cells via upregulation of c-Fos,c-Jun,c-Myc,and HPV16 E6 and E7 expressions.
基金Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects,No.Z202000962023 Guangxi University Young and Middle-Aged Teachers’Basic Research Ability Improvement Project,No.2023KY0091+1 种基金National Natural Science Foundation of China,No.82260241the Natural Science Foundation of Guangxi Province,No.2015GXNSFAA139171 and No.2020GXNSFAA259053.
文摘BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.
基金Supported by Wu Jieping Medical Foundation,No.320.6750.2022-20-25and Chongqing Health Commission,No.[2020]68.
文摘BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.
基金supported by the Taipei Tzu Chi Hospital through grants from the Buddhist Tzu Chi Medical Foundation under the Numbers TCRD-TPE-111-23(2/3)and TCRD-TPE-113-20,Taipei,Taiwan.
文摘Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.
文摘There was no detectable expression of c-fos,but a little c-myc,high c-fms and mederate high IGF-ⅡmRNA in the untreated human hepatocarcinoma cell SMMC- 7721.After treatment with 10 μmol/L retinoic acid or 0.5 mmol/L dibutyryl cyclic-3',5'adenosine monophosphate(db-cAMP),the c-fos was transiently expressed within 20- 60mins.If the treatment of RA or db-cAMP prolonged to 1-5 days, the transcriptions of c- myc were increased,reaching the highest level on the 2nd and 4th day.Simultaneously the transcriptions of c- fms and IGF- Ⅱwere gradually decreased.On the 5th day of the treatment,c-fms and IGF-ⅡmRNA were decreased to 32% and 14%respectively of the control (untreated cell) value by RA,and 35% and 22%respectively by db-cAMP.The biological significance of the above mentioned results was discussed.
文摘Expression of oncogene and anti-oncogene products in 12 cases of male breast carcinoma was studied.Positive staining was seen in 6 cases for c-myc,6 cases for EGFR.4 cases for c-erbB-2 cases for N-ras,5 cases for Rb and 3 cases for P53.One case was positive and 4 cases were negative for all above mentioned oncogene and antioncogene products.In addition,Cathepsin D(Cath-D),ER.PR,AR.PCNA and AgNOR were also assayed.In all the cases showed c-erbB-2 or P53 positive were Cath-D positive.The significance of expression of c-erbB-2,c-myc,Cath-D,ER and PR in male breast carcinoma was emphatically discussed.
文摘Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instead integrate their genetic material into the host genome thus,affecting cell cycle and tumor suppression.This deregulation also leads to impaired immune function and promotes tumor progression by disrupting the removal of infected cells.Generally,innate immunity consists of two important members,including mitochondria and cell deaths,which impact each other as well.Due to the close correlation between viruses,cell death pathways(apoptosis,necroptosis,and pyroptosis),and mitochondria(mitochondrial antiviral-signaling protein and reactive oxygen species generation),targeting these immune system representatives may offer therapeutic strategies to control the progression of oncogenic viral infections.Some previous studies have covered the association of oncogenic viruses with mitochondria and cell death pathways,respectively,but mitochondria and cell death interact with each other,separately,and this interaction may play a role in the progression of cancer induced by oncogenic viruses.Hence,the purpose of this review is to discuss the relationship between cell death,mitochondria,and viral oncogenesis,focusing on the most surveyed oncogenic viruses’mechanisms of action.
文摘Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal ma-lignancies with limited treatment efficacy.Advances in precision oncology,enabled by next-generation sequencing,have highlighted key molecular targets.Kirsten rat sarcoma viral oncogene homolog mutations,present in up to 90%of cases,drive aggressive biology,though most variants remain undruggable;allele-specific inhibitors and exosome-based RNA interference are under exploration.Breast cancer susceptibility gene 1/2 mutations occur in 4%-7%of patients,con-ferring sensitivity to platinum agents and poly(ADP-ribose)polymerase inhi-bitors.Other rare but actionable alterations-such as v-raf murine sarcoma viral oncogene homolog B1(V600),neurotrophic tyrosine receptor kinase,fibroblast growth factor receptor 2,and RET fusions-show benefit in tumor-agnostic trials,broadening options for selected subgroups.Immunotherapy is limited,as high tumor mutational burden and mismatch repair deficiency are uncommon in PDAC,though predictive when present.Co-mutations in tumor protein p53,cyclin-dependent kinase inhibitor 2A,and SMAD4 further stratify prognosis and influence therapy response.Cross-cancer analyses underscore the necessity of PDAC-specific strategies despite shared genomic drivers.Collectively,these insights support routine germline and somatic testing,enrollment in biomarker-matched trials,and rational combination strategies,establishing molecular profiling as central to advancing precision treatment in pancreatic cancer.
文摘This editorial comments on the review by Da Silva et al,published in the World Journal of Clinical Oncology which focuses on the molecular perspectives of lung cancer.With the rapid development of molecular technology,new diagnostic methods are constantly emerging,including liquid biopsy,the identification of gene mutations,and the monitoring biomarkers,thus providing precise in-formation with which to identify the occurrence and development of lung cancer.Biomarkers,such as circulating tumor cells,circulating tumor DNA,and cir-culating RNA can provide helpful information for clinical application.Common types of genetic mutations and immune checkpoints include epidermal growth factor receptor,anaplastic lymphoma kinase,c-ROS proto-oncogene 1,progra-mmed death-1 and cytotoxic T-lymphocyte-associated protein.According to specific biomarkers,targeted therapy and immunotherapy can improve survival outcomes based on the types of gene mutation and immune checkpoints.The application of molecular approaches can facilitate our ability to control the progression of disease and select appropriate therapeutic strategies for patients with lung cancer.
基金supported by grants from Guangxi Nanning Qingxiu District Key Research and Development Program of Science and Technology Plan(no.2020050)Guangxi Medical and Health Appropriate Technology Development,Promotion and Application Project(no.S2021097)+1 种基金Guangxi Key Research and Development Program(no.AB22080064)Guangxi Natural Science Foundation(no.2017GXNSFAA198126).
文摘Objective To evaluate the expression pattern of non-SMC condensin II complex subunit D3(NCAPD3)in hepatocellular carcinoma(HCC)tissues,assess its association with clinical characteristics,and explore the effects of NCAPD3 on HCC cells and the potential underlying mechanisms.Methods NCAPD3 expression in HCC tumors and adjacent noncancerous tissues was quantified via quantitative PCR.Patients were divided into high-and low-expression groups on the basis of NCAPD3 levels,and associations with clinical parameters were assessed.The effects of NCAPD3 knockdown and the phosphatidylinositol-3-kinase(PI3K)agonist Y-P 740 on cell functions were examined via cell proliferation,Transwell migration,and invasion assays.Differentially expressed genes following NCAPD3 knockdown in SMMC-7721 cells were identified via mRNA sequencing.Western blotting was performed to measure NCAPD3,AKT serine/threonine kinase 1(AKT1),and phosphorylated AKT1 levels.Results NCAPD3 mRNA expression was notably upregulated in HCC tissues as compared with that in adjacent noncancer tissues.A positive correlation was observed between NCAPD3 expression and both lymphatic and distant metastases in patients with HCC.NCAPD3 knockdown reduced the proliferation and metastasis of SMMC-7721 and Huh-7 cells.mRNA sequencing revealed 140 downregulated genes and 125 upregulated genes.Further validation experiments confirmed that NCAPD3 modulated the PI3K-AKT signalling pathway and that the PI3K agonist Y-P 740 counteracted the effects of NCAPD3 knockdown.Conclusions Elevated NCAPD3 expression was strongly correlated with HCC metastasis.NCAPD3 inhibition impedes HCC cell growth and metastatic potential by suppressing the PI3K–AKT signalling pathway.
文摘The heat sensitivity of Human gingival squamous carcinoma Ca9-22 cells with oncogene erbB-1/EGFR and Chinese hamster V79 cells of normal thermosensitivity as control was investigated.Colony forming ability of the treated cells was assayed in vitro. Heat-treatment period-survival and the concerned curves were drawn.The slopes of exponentially regressing parts of the survival curves were estimated in the TO values of cellular thermosensitivity and subjected to Arrhenius analysis-The 42-44℃ time-survival curves of Ca9-22 cells showed biphasic slopes which indicated the presence of thermotolerance induction during continuous heating even at 44℃ while for the V79 cells the biphasic slopes due to thermotolerance induction were shown in temperatures at and before 42℃. In comparison of TO values with V79 cells, those of Ca9-22 cells were longer (less thermosensitive) by about 2.1 fold at 43℃ and 1-2 fold at 44℃. Both V79 and Ca9-22 cells were sensitized by 44--42℃ step-down heating (SDH).42℃ beat treatment period-survival curves of 44℃ ( 5minute) preheated V79 cells; while Ca9-22 cells under the same treatment condition for not only 5 minutes but 20 minutes showed biphasic slope, which indicated the Presence of thermotolerance. The thermosensitization ratio (TSR) of Ca9-22 cells were smaller than V79 cells.Arrhenius curves a breaking points at 44℃ and 43℃ for Ca9-22 and V79 cells, respectively. The activation energies of V79 cells were 145kcallmole and 400kcal/mole above and below 43℃ (p < 0.05), respectively,while those of Ca9-22 cells were 200 kcal/mole and 250kcal/mole above and below 44℃ (P <0.05), respectively.These data suggested that oncogene erbB-1 /EGFRcontained in Ca9-22 cells may contribute to reducethermosensitivity and variety in term of G￣1 phase as shown in fractionated Hydroxyurea treatment.
文摘Lipid metabolism plays a pivotal role in gastric cancer(GC)progression,characterized by complex metabolic reprogramming that supports tumor growth and survival.This narrative review comprehensively examines the dysregulation of lipid metabolism-associated genes,including fatty acid synthase(FASN),ATPcitrate lyase,acetyl-CoA carboxylases,FA binding proteins,sterol regulatory element-binding proteins,and other key enzymes.These genes facilitate critical oncogenic processes by enhancing FA synthesis,modifying cellular signaling,and supporting cancer cell proliferation,migration,and therapy resistance.Metabolic adaptations observed in GC include increased de novo lipogenesis,altered enzymatic activities,and modified protein lipidation,which contribute to tumor aggressiveness.The review highlights the potential of targeting these metabolic pathways as a therapeutic strategy,demonstrating how inhibiting specific enzymes like FASN,ATP-citrate lyase,and stearoyl-CoA desaturase 1 can induce apoptosis,disrupt cancer stem cell properties,and potentially overcome treatment resistance.By elucidating the intricate interactions between lipid metabolism genes and cancer progression,this review provides insights into novel diagnostic and therapeutic approaches for managing GC.
基金Project supported by the zhejiang Natural Scierce Fundation No.925006.
文摘AIM To study the significance of C-erbB-2 oncogene amplification in gastric cancer.METHODS C-erbB-2 oncogene amplification was examined by using differential polymerase chain reaction (dPCR) in surgical and endoscopic specimens of 83 cases of gastric cancer and 101 metastatic lymph nodes.RESULTS C-erbB-2 amplification was found in 28.9% (24/ 83) surgical specimens and 20.5% (17/ 83) endoscopic ones of gastric cancer patients. The amplification was significant in both types of specimens of advanced cancer cases (P＜0.05) and surgical specimens with lymph node metastasis (P＜0.01). The incidence of C-erbB-2 amplification in lymph nodes with metastasis was higher than in primary sites (surgical specimens, P＜0.05). The patients with amplification tumors had poorer 5-year survival rates than those with unamplification ones in the early cancers and well to moderately differentiated adenocarcinomas (P＜0.05). The same surgical samples were tested again by Southern blot hybridization to ascertain C-erbB-2 amplification, and the positive rate of C-erbB-2 amplification (15.7%) was lower than that of dPCR (28.9%, P＜0.05).CONCLUSION Examining C-erbB-2 amplification by dPCR is a quick, simple, reliable and independent method, and is helpful in predicting prognosis and metastatic potential of gastric cancer.
基金Supported by the Major Programs of Guangzhou University of TCM and the National Key Technologies Research and Development Program of China during the 8th Five-Year Plan Period, No. GH0016 and 85-919-01-01
文摘AIM: To observe the protein and mRNA expression of bcl-2 oncogene in gastric precancerous lesions (GPL) and to analyze its correlation with syndromes in traditional Chinese medicine (TCM). METHODS: Sixty-seven patients with GPL confirmed by gastroscopy and pathology were studied,including 39 cases of moderate gastric mucosal dysplasia,19 cases of severe gastric mucosa dysplasia, 9 cases of incomplete colon metaplasia. In syndrome differentiation of TCM,17 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by qi stagnation, 21 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by stomach heat, 29 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by blood stasis. Protein and mRNA expression of bcl-2 oncogene were detected by labeled streptavidin biotin (LSAB) immunohist-ochemistry and in situ hybridization respectively. RESULTS: Abnormal expression of protein and mRNA on bcl-2 oncogene was found in GPL,which increased gradually with the course of lesions. In moderate and severe gastric mucosal dysplasia and incomplete colon metaplasia,there was no difference in the expression of bcl-2 oncogene (P>0.05).In different accompanying syndromes, the expression of protein and mRNA on bcl-2 oncogene increased gradually in the following order: deficiency of both qi and yin of the spleen and stomach accompanying qi stagnation→stomach heat→blood stasis. In GPL, compared with accompanying blood stasis, there was an obvious difference in the expression of bcl-2 oncogene between the syndrome of qi and yin deficiency of the spleen and stomach and accompanying stomach heat, so did accompanying qi stagnation (the level of protein: X2=8.45, P<0.05;the level of mRNA: X2=7.35, P<0.05). CONCLUSION: Apoptosis-associated bcl-2 oncogene is abnormally expressed in GPL,which correlates with different accompanying syndromes in TCM.
基金Supported by Natural Science Foundation of Shaanxi Province(Grant No.2018722)
文摘Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of CSCC.The difference was statistically significant(X^2=7.26.P=0.001<0.05).While expression of c-fos protein was positively related to differentiation of CSCC.which was statistically significant(X^2=7.47,P=0.0012<0.025).Conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of CSCC differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.
文摘Sustained expression of the Spi-1/PU.1 and Fli-1 oncoproteins blocks globin gene activation in mouse erythroleukemia cells; however, only Spi-1/PU.1 expression inhibits the inclusion of exon 16 in the mature 4.1R mRNA. This splicing event is crucial for a functional 4.1R protein and, therefore, for red blood cell membrane integrity. This report demonstrates that Spi-1/PU.1 downregulation induces the activation of TRIM10/hematopoietic RING finger 1 （HERF1）, a member of the tripartite motif （TRIM）/RBCC protein family needed for globin gene transcription. Additionally, we demonstrate that TRIM10/HERF1 is required for the regulated splicing of exon 16 during late erythroid differentia- tion. Using inducible overexpression and silencing approaches, we found that： （1） TRIM10/HERF1 knockdown inhibits hemoglobin production and exon splicing and triggers cell apoptosis in dimethylsulfoxide （DMSO）-induced cells; （2） TRIM10/HERF1 upregulation is required but is insufficient on its own to activate exon retention; （3） Fli-1 has no effect on TRIM10/HERFI expression, whereas either DMSO-induced downregulation or shRNA-knockdown of Spi-I/PU.I expression is sufficient to activate TRIM10/HERF1 expression; and （4） Spi-1/PU.1 knockdown triggers both the transcription and the splicing events independently of the chemical induction. Altogether, these data indicate that primary Spi-1/PU.1 downregulation acts on late erythroid differentiation through at least two pathways, one of which requires TRIM10/HERF1 upregulation and parallels the Spi-1/PU.1-induced Fli-1 shutoff regulatory cascade.
基金This study was supported by grants from the National Outstanding YouthFoundation of China (type B, No. 3982511 ) and the Provincial NaturalScience Foundation of Guangdong, China (No. 980107)
文摘BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.
文摘Objective: To explore the expression of c-Met mRNA in nasopharyngeal carcinomas (NPC) and its relation with clinical biological behavior. Methods: In situ hybridisation was used to detect mRNA expression of c-Met in 15 cases of non-tumor nasopharyngeal (NP), 55 cases of NPC. Results: The positive rates of c-Met mRNA in NP and NPC cells were 13.3% (2/15) and 61.8% (34/55) respectively. The expression of c-Met mRNA was significantly correlated with lymph node metastasis, local invasion (skull base erosion), and clinical stage. In cases with cervical lymph node metastasis, local invasion, and clinical stage III and IV (UICC), the positive rates of expression of c-Met mRNA were significantly higher than that in those without the conditions mentioned above (P < 0.05 or P < 0.01). But it was not significantly correlated with age, gender, histo- logic grade, and cranial nerve palsy (P > 0.05). Conclusion: The abnormal expression of c-Met gene was well correlated with the biological behavior of metastasis and invasion. To detection the expression of c-Met mRNA could serve as an important index to estimate the prognosis of NPC. C-Met may be a new diagnostic/therapeutic target of NPC.
