Aiming to address the Unmanned Aerial Vehicle(UAV) formation collision avoidance problem in Three-Dimensional(3-D) low-altitude environments where dense various obstacles exist, a fluid-based path planning framework n...Aiming to address the Unmanned Aerial Vehicle(UAV) formation collision avoidance problem in Three-Dimensional(3-D) low-altitude environments where dense various obstacles exist, a fluid-based path planning framework named the Formation Interfered Fluid Dynamical System(FIFDS) with Moderate Evasive Maneuver Strategy(MEMS) is proposed in this study.First, the UAV formation collision avoidance problem including quantifiable performance indexes is formulated. Second, inspired by the phenomenon of fluids continuously flowing while bypassing objects, the FIFDS for multiple UAVs is presented, which contains a Parallel Streamline Tracking(PST) method for formation keeping and the traditional IFDS for collision avoidance. Third, to rationally balance flight safety and collision avoidance cost, MEMS is proposed to generate moderate evasive maneuvers that match up with collision risks. Comprehensively containing the time and distance safety information, the 3-D dynamic collision regions are modeled for collision prediction. Then, the moderate evasive maneuver principle is refined, which provides criterions of the maneuver amplitude and direction. On this basis, an analytical parameter mapping mechanism is designed to online optimize IFDS parameters. Finally, the performance of the proposed method is validated by comparative simulation results and real flight experiments using fixed-wing UAVs.展开更多
Neuropathic pain(NP)is one of the most common pathological pain types and is associated with limited treatment options;moreover,it affects patients’quality of life and causes a heavy social burden.Despite the emphasi...Neuropathic pain(NP)is one of the most common pathological pain types and is associated with limited treatment options;moreover,it affects patients’quality of life and causes a heavy social burden.Despite the emphasis on inhibiting neuronal apoptosis to relieve NP,the crucial role of a neuroinflammation is often overlooked.Therefore,refocusing on the regulation of microglia polarization to create a more conducive environment for neuron holds great potential in NP treatment.In recent years,small interfering RNAs(siRNAs)had become an attractive therapeutic option.However,an efficient loading and delivery system for siRNA is still in lack.In our study,a nanostructured tetrahedral framework nucleic acid loaded with the small interfering RNA C–C chemokine receptor 2(T-siCCR2)was successfully designed and synthesized for use in NP rat model in vivo and in a lipopolysaccharide(LPS)-induced inflammatory environment in vitro.This nanoscale complex is endowed with structural stability and satisfactory delivery efficiency while assuring the silencing effect of siRNA-CCR2.In vivo,T-siCCR2 treatment exhibited favorable effects on pain relief and functional improvement in the NP animal model by directly targeting microglia.In vitro,T-siCCR2 counteracts LPS-induced inflammation by inhibiting the differentiation of microglia toward the M1 phenotype,thus playing a neuroprotective role.RNA sequencing was subsequently performed to elucidate the underlying mechanism involved.These results indicate that T-siCCR2 may serve as a potential treatment option for NP in the future.展开更多
RNA interference(RNAi)is a post-transcriptional gene-silencing technique induced by the introduction of double-stranded RNA(dsRNA)or small interfering RNA(siRNA)[1].RNAi-based strategies have been extensively applied ...RNA interference(RNAi)is a post-transcriptional gene-silencing technique induced by the introduction of double-stranded RNA(dsRNA)or small interfering RNA(siRNA)[1].RNAi-based strategies have been extensively applied in the treatment of human diseases and crop protection against insect pests[2-4].With the availability of the full genome sequences of major mosquito vectors,RNAi has become increasingly used as a novel means of mosquito control[5].展开更多
We present a compact optical delay line(ODL)with wide-range continuous tunability on thin-film lithium niobate platform.The proposed device integrates an unbalanced Mach-Zehnder interferometer(MZI)architecture with du...We present a compact optical delay line(ODL)with wide-range continuous tunability on thin-film lithium niobate platform.The proposed device integrates an unbalanced Mach-Zehnder interferometer(MZI)architecture with dual tunable couplers,where each coupler comprises two 2×2 multimode interferometers and a MZI phase-tuning section.Experimental results demonstrate continuous delay tuning from 0 to 293 ps through synchronized control of coupling coefficients,corresponding to a 4 cm path difference between interferometer arms.The measured delay range exhibits excellent agreement with theoretical predictions derived from ODL waveguide parameters.This result addresses critical challenges in integrated photonic systems that require precise temporal control,particularly for applications in optical communications and quantum information processing,where a wide tuning range is paramount.展开更多
Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ische...Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.展开更多
In order to assist the design of short interfering ribonucleic acids （siRNA）, 573 non-redundant siRNAs were collected from published literatures and the relationship between siRNAs sequences and RNA interference （R...In order to assist the design of short interfering ribonucleic acids （siRNA）, 573 non-redundant siRNAs were collected from published literatures and the relationship between siRNAs sequences and RNA interference （RNAi） effect is analyzed by a support vector machine （SVM） based algorithm relied on a basebase correlation （BBC） feature. The results show that the proposed algorithm has the highest area under curve （AUC） value （0. 73） of the receive operating characteristic （ROC） curve and the greatest r value （0. 43） of the Pearson＇s correlation coefficient. This indicates that the proposed algorithm is better than the published algorithms on the collected datasets and that more attention should be paid to the base-base correlation information in future siRNA design.展开更多
Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the firs...Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.展开更多
AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was ...AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line,BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1,pGPU6-2,pGPU6-3 and pGPU6-4,and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry,respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers.RESULTS:The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect,followed by pGPU6-2 and pGPU6-3 groups.Invasiveness and adhesion were more significantly reduced in pGPU6-1,pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However,no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups.CONCLUSION:RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line,BxPC-3,leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor.展开更多
Hepatocellular carcinoma(HCC) is the 5th most common malignancy which is responsible for more than half million annual mortalities; also, it is the third leading cause of cancer related death. Unfavorablesystemic side...Hepatocellular carcinoma(HCC) is the 5th most common malignancy which is responsible for more than half million annual mortalities; also, it is the third leading cause of cancer related death. Unfavorablesystemic side-effects of chemotherapeutic agents and susceptibility to the degradation of small interfering RNAs(si RNAs), which can knock down a specific gene involved in the disease, have hampered their clinical application. So, it could be beneficial to develop an efficient carrier for the stabilization and specific delivery of drugs and si RNA to cells. Targeted nanoparticles have gained considerable attention as an efficient drug and gene delivery system, which is due to their capability in achieving the highest accumulation of cytotoxic agents in tumor tissue, modifiable drug pharmacokinetic- and bio-distribution, improved effectiveness of treatment, and limited sideeffects. Recent studies have shed more light on the advantages of novel drug loaded carrier systems vs free drugs. Most of the animal studies have reported improvement in treatment efficacy and survival rate using novel carrier systems. Targeted delivery may be achieved passively or actively. In passive targeting, no ligand as homing device is used, while targeting is achieved by incorporating the therapeutic agent into a macromolecule or nanoparticle that passively reaches the target organ. However, in active targeting, the therapeutic agent or carrier system is conjugated to a tissue or cell-specific receptor which is overexpressed in a special malignancy using a ligand called a homing device. This review covers a broad spectrum of targeted nanoparticles as therapeutic and nonviral si RNA delivery systems, which are developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and their characteristics and opportunities for the clinical applications of drugs and therapeutic si RNA are discussed in this article. Asialoglycoprotein receptors, low-density lipoprotein, ganglioside GM1 cell surface ligand, epidermal growth factor receptor receptors, monoclonal antibodies, retinoic acid receptors, integrin receptors targeted by Arg-Gly-Asp peptide, folate, and transferrin receptors are the most widely studied cell surface receptors which are used for the site specific delivery of drugs and si RNA-based therapeutics in HCC and discussed in detail in this article.展开更多
Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expressi...Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expression of microRNAs(miRNAs)is significantly related to gastric cancer tumor stage,size,differentiation and metastasis.MiRNAs interrupt cellular signaling pathways,inhibit the activity of tumor suppressor genes,and affect the cell cycle in gastric cancer cells.Some miRNAs,including miR-21,miR-106a and miR-421,could be potential markers for the diagnosis of gastric cancer.Long non-coding RNAs (lncRNAs),a new research hotspot among cancerassociated ncRNAs,play important roles in epigenetic,transcriptional and post-transcriptional regulation.Several gastric cancer-associated lncRNAs,such as CCAT1,GACAT1,H19,and SUMO1P3,have been explored.In addition,Piwi-interacting RNAs,another type of small ncRNA that is recognized by gastroenterologists,are involved in gastric carcinogenesis,and piR-651/823represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice.Small interfering RNAs also function in posttranscriptional regulation in gastric cancer and might be useful in gastric cancer treatment.展开更多
Objective:To observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein rnRNA in the bone marrow,peripheral blood and nasal lavage fluid.Mc...Objective:To observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein rnRNA in the bone marrow,peripheral blood and nasal lavage fluid.Mctliods:Twenty-four BALB/c mice were randomly divided into the control group.PBS therapy group.siKNA therapy group and the CCR3 siRNA therapy group(n=6).Allergic rhinitis model were sensitized and stimulated by ovalbunfin,and CCR3 siKNA therapy group were administered with CCH3 transnasally before stimulated.The levels of the eosinophils CCR3.MBP.ECP and EPO in bone marrow,peripheral blood and nasal lavage fluid were detected by RT-PCR.Results:Compared to the control group and CCR3 siR.NA therapy group,the nasal mucosa of the PBS therapy group and siRNA therapy group developed epithalaxy.goblet cells hyperplasia,squamous epithelium metaplasia,epithelium necrosis,lamina propria and submucosa gland hyperplasia,vasodilatation,tissue edema,and the characterized eosinophil infiltration.RT-PCR indicated that the CCR3 rnRNA,MBP.ECP and EPC)expression in bone marrow,peripheral blood and nasal lavage fluid of the CCR3 siKNA therapy group was lower than the PBS therapy group and siR.NA therapy group(P<0.05).Conclusions:The RNA interference therapy to CCR3 by local administration pernasal can suppress the process of the development,migration and invasion of the allergic rhinitis eosinophil,thus can reduce the effect of eosinophils and then reduce the inflammation effect of the allergic rhinitis.It may be a new treatment for respiratory tract allergic inflammation.展开更多
AIM:To investigate the expression of vascular endothelial cell growth factor (VEGF) and its receptors Fmslike tyrosine kinase 1 (FLT-1) and fetal liver kinase 1 (FLK-1) in colorectal carcinoma (CRC),and the blocking e...AIM:To investigate the expression of vascular endothelial cell growth factor (VEGF) and its receptors Fmslike tyrosine kinase 1 (FLT-1) and fetal liver kinase 1 (FLK-1) in colorectal carcinoma (CRC),and the blocking effects of small interfering RNAs (siRNAs) on VEGF expression in human colorectal cancer HCT116 cells.METHODS:Immunohistochemical staining for VEGF,FLT-1 and FLK-1 proteins was performed in 82 cases of CRC and 14 normal colorectal mucosae.A siRNA targeting VEGF was synthesized and transfected into HCT116 cells using lipofectamine 2000.Immunocytochemical staining and Western blotting analyses were performed to detect the expression of VEGF protein.The suppressive effect of the siRNA on cell proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltertrazolium bromide (MTT) assay.Cellular apoptosis was detected using flow cytometry (FCM).RESULTS:The expression of VEGF,FLT-1 and FLK-1 in tumor tissues was significantly higher than that in normal tissues (P=0.008,P=0.000,P=0.000).The expression of VEGF was positively correlated with both lymph node metastasis and clinical stage (P=0.009 and P=0.025,respectively).Immunocytochemistry showed that the expression of VEGF was weakly positive and Western blotting indicated a significant reduction in VEGF-siRNA cell protein levels.VEGF-siRNA cell growth inhibition was assessed by the MTT assay,and the tumor cell proliferation rate was significantly different at 24,48,and 72 h after transfection.FCM results showed that the VEGF-siRNA group had an apparent aneuploid peak.CONCLUSION:VEGF,FLT-1 and FLK-1 are associated with colorectal carcinogenesis.siRNA silencing of the VEGF gene suppresses proliferation,and induces apoptosis in HCT116 cells.The results suggest that VEGF may be a new gene therapy target for colorectal cancer.展开更多
RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, p...RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, providing a potentially effective platform for the treatment of a wide array of diseases. However, similar to other nucleic acid-based drugs,the major hurdle of RNAi therapy is lack of efficient and non-immunogenic delivery vehicles. Currently, viruses, synthetic polymers, and lipid-based carriers are among the most widely studied vehicles for small RNA delivery. However, many drawbacks are reported to be associated with these delivery vehicles. There is a pressing need to replace them with more efficient and better-tolerated approaches. Exosomes secreted from the endocytic compartment of live cells, are a subtype of endogenous extracellular vesicles that transfer genetic and biochemical information among different cells, thus playing an important role in cellcell communication. Recently, accumulating attention has been focused on harnessing exosomes as nanaocarriers for small RNAs delivery. Due to their natural role in shuttling endogenous nucleic acid in our body, exosomes may exhibit higher delivery efficiency, lower immunogenicity, and better compatibility than existing foreign RNA carriers. Importantly,exosomes own intrinsic homing capacity that can guide small RNAs across natural membranous barriers. Moreover, such a capacity can be further improved by adding appropriate targeting moieties. In this manuscript, we briefly review the progress and challenges of RNAi therapy, and discuss the potential of exosomes' applications in small RNA delivery with focus on the most recent advances in exosome-based small RNA delivery for disease therapy.展开更多
RNA interference (RNAi) is triggered by the presence of a double-stranded RNA (dsRNA), and results in the silencing of homologous gene expression through the specific degradation of an mRNA containing the same sequenc...RNA interference (RNAi) is triggered by the presence of a double-stranded RNA (dsRNA), and results in the silencing of homologous gene expression through the specific degradation of an mRNA containing the same sequence. dsRNAmediated RNAi can be used in a wide variety of eucaryotes to induce the sequence-specific inhibition of gene expression.Synthetic 21-23 nucleotide (nt) small interfering RNA (siRNA) with 2 nt 3' overhangs was recently found to mediate efficient sequence-specific mRNA degradation in mammalian cells. Here, we studied the effects of synthetic siRNA duplexes targeted to SARS coronavirus structural proteins E, M, and N in a cell culture system. Among total 26 siRNA duplexes, we obtained 3 siRNA duplexes which could sequence-specifically reduce target genes expression over 80％ at the concentration of 60 nM in Vero E6 cells. The downregulation effect was in correlation with the concentrations of the siRNA duplexes in a range of 0～60 nM. Our results also showed that many inactive siRNA duplexes may be brought to life simply by unpairing the 5' end of the antisense strands. Results suggest that siRNA is capable of inhibiting SARS coronavirus genes expression and thus may be a new therapeutic strategy for treatment of SARS.展开更多
AIM: To further analyse cancer involvement of basic transcription factor 3 (BTF3) after detection of its upregulation in gastric tumor samples. METHODS: BTF3 transcription rates in human gastric tumor tissue samples (...AIM: To further analyse cancer involvement of basic transcription factor 3 (BTF3) after detection of its upregulation in gastric tumor samples. METHODS: BTF3 transcription rates in human gastric tumor tissue samples (n = 20) and adjacent normal tissue (n = 18) specimens as well as in the gastric cancer cell lines AGS, SGC-7901, MKN-28, MKN-45 and MGC803 were analyzed via quantitative real-time polymerase chain reaction. The effect of stable BTF3 silencing via infection with a small interfering RNA (siRNA)-BTF3 expressing lentivirus on SGC-7901 cells was measured via Western blotting analysis, proliferation assays, cell cycle and apoptosis profiling by flow cytometry as well as colony forming assays with a Cellomic Assay System. RESULTS: A significant higher expression of BTF3 mRNA was detected in tumors compared to normal gastric tissues (P < 0.01), especially in section tissues from female patients compared to male patients, and all tested gastric cancer cell lines expressed high levels of BTF3. From days 1 to 5, the relative proliferation rates of stable BTF3-siRNA transfected SGC7901 cells were 82%, 70%, 57%, 49% and 44% compared to the control, while the percentage of cells arrested in the G 1 phase was significantly decreased (P = 0.000) and the percentages of cells in the S (P = 0.031) and G 2 /M (P = 0.027) phases were significantly increased. In addition, the colony forming tendency was significantly decreased (P = 0.014) and the apoptosis rate increased from 5.73% to 8.59% (P = 0.014) after BTF3 was silenced in SGC7901 cells. CONCLUSION: BTF3 expression is associated with enhanced cell proliferation, reduced cell cycle regulation and apoptosis and its silencing decreased colony forming and proliferation of gastric cancer cells.展开更多
AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 norm...AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.展开更多
AIM:To investigate the function of gamma-aminobutyric acid(GABA)and gamma-aminobutyric acid A receptorθsubunit(GABRQ)in hepatocellular carcinoma(HCC).METHODS:Semiquantitative polymerase chain reaction was used for de...AIM:To investigate the function of gamma-aminobutyric acid(GABA)and gamma-aminobutyric acid A receptorθsubunit(GABRQ)in hepatocellular carcinoma(HCC).METHODS:Semiquantitative polymerase chain reaction was used for detecting the expression of GABRQ receptor among HCC cell line HepG2,normal liver cell line L-02,non-malignant Chang's liver cells,8 samples of HCC tissues and paired non-cancerous tissues.HepG2 cells were treated with GABA at serial concentrations(0,1,10,20,40 and 60μmol/L),and their proliferating abilities were analyzed with the methyl thiazolyl tetrazolium assay,cell cycle analysis and tumor implanted in nude mice.Small interfering RNA was used for knocking down the endogenous GABRQ in HepG2.Proliferating abilities of these cells treated with or without GABA were analyzed.RESULTS:We identified the overexpression of GABRQ in HCC cell lines and half of the tested HCC tissues.Knockdown of endogenous GABRQ expression in HepG2 attenuated HCC cell growth,suggesting its role in HCC cell viability.We studied the effect of GABA in the proliferation of GABRQ-positive cell lines in vitro and in vivo,and found that GABA increased HCC growth in a dosedependent manner.Notably,the addition of GABA into the cell culture medium promoted the proliferation of GABRQ-expressing HepG2 cells,but not GABRQ-knockdown HepG2 cells,which means that GABA stimulates HepG2 cell growth through GABRQ.CONCLUSION:GABRQ play important roles in HCC development and progression and could be a promising molecular target for the development of new diagnostic and therapeutic strategies of HCC.展开更多
基金supported in part by the National Natural Science Foundations of China(Nos.61175084,61673042 and 62203046)the China Postdoctoral Science Foundation(No.2022M713006).
文摘Aiming to address the Unmanned Aerial Vehicle(UAV) formation collision avoidance problem in Three-Dimensional(3-D) low-altitude environments where dense various obstacles exist, a fluid-based path planning framework named the Formation Interfered Fluid Dynamical System(FIFDS) with Moderate Evasive Maneuver Strategy(MEMS) is proposed in this study.First, the UAV formation collision avoidance problem including quantifiable performance indexes is formulated. Second, inspired by the phenomenon of fluids continuously flowing while bypassing objects, the FIFDS for multiple UAVs is presented, which contains a Parallel Streamline Tracking(PST) method for formation keeping and the traditional IFDS for collision avoidance. Third, to rationally balance flight safety and collision avoidance cost, MEMS is proposed to generate moderate evasive maneuvers that match up with collision risks. Comprehensively containing the time and distance safety information, the 3-D dynamic collision regions are modeled for collision prediction. Then, the moderate evasive maneuver principle is refined, which provides criterions of the maneuver amplitude and direction. On this basis, an analytical parameter mapping mechanism is designed to online optimize IFDS parameters. Finally, the performance of the proposed method is validated by comparative simulation results and real flight experiments using fixed-wing UAVs.
基金supported by National Natural Science Foundation of China(Nos.81874027,82370929,81970916)Sichuan Science and Technology Program(Nos.2019YFQ0003,2022YFS0051,2022NSFSC0002)+3 种基金Sichuan Province Youth Science and Technology Innovation Team(No.2022JDTD0021)Research and Develop Program,West China Hospital of Stomatology Sichuan University(Nos.RD03202302,RCDWJS2024–1)135-project for disciplines of excellenceClinical Research Incubation project of West China Hospital of Sichuan University(No.2021HXFH036)。
文摘Neuropathic pain(NP)is one of the most common pathological pain types and is associated with limited treatment options;moreover,it affects patients’quality of life and causes a heavy social burden.Despite the emphasis on inhibiting neuronal apoptosis to relieve NP,the crucial role of a neuroinflammation is often overlooked.Therefore,refocusing on the regulation of microglia polarization to create a more conducive environment for neuron holds great potential in NP treatment.In recent years,small interfering RNAs(siRNAs)had become an attractive therapeutic option.However,an efficient loading and delivery system for siRNA is still in lack.In our study,a nanostructured tetrahedral framework nucleic acid loaded with the small interfering RNA C–C chemokine receptor 2(T-siCCR2)was successfully designed and synthesized for use in NP rat model in vivo and in a lipopolysaccharide(LPS)-induced inflammatory environment in vitro.This nanoscale complex is endowed with structural stability and satisfactory delivery efficiency while assuring the silencing effect of siRNA-CCR2.In vivo,T-siCCR2 treatment exhibited favorable effects on pain relief and functional improvement in the NP animal model by directly targeting microglia.In vitro,T-siCCR2 counteracts LPS-induced inflammation by inhibiting the differentiation of microglia toward the M1 phenotype,thus playing a neuroprotective role.RNA sequencing was subsequently performed to elucidate the underlying mechanism involved.These results indicate that T-siCCR2 may serve as a potential treatment option for NP in the future.
基金supported by grants from the National Key Research and Development Program(2023YFE0113600).
文摘RNA interference(RNAi)is a post-transcriptional gene-silencing technique induced by the introduction of double-stranded RNA(dsRNA)or small interfering RNA(siRNA)[1].RNAi-based strategies have been extensively applied in the treatment of human diseases and crop protection against insect pests[2-4].With the availability of the full genome sequences of major mosquito vectors,RNAi has become increasingly used as a novel means of mosquito control[5].
基金supported by the National Natural Science Foundation of China(Grant Nos.12192251,12334014,12404378,92480001,12134001,12174113,12174107,12474325,12404379,and 12474378)the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0301403)+1 种基金Shanghai Municipal Science and Technology Major Project(Grant No.2019SHZDZX01)Fundamental Research Funds for the Central Universities,the Engineering Research Center for Nanophotonics&Advanced Instrument,Ministry of Education,East China Normal University(Grant No.2023nmc005).
文摘We present a compact optical delay line(ODL)with wide-range continuous tunability on thin-film lithium niobate platform.The proposed device integrates an unbalanced Mach-Zehnder interferometer(MZI)architecture with dual tunable couplers,where each coupler comprises two 2×2 multimode interferometers and a MZI phase-tuning section.Experimental results demonstrate continuous delay tuning from 0 to 293 ps through synchronized control of coupling coefficients,corresponding to a 4 cm path difference between interferometer arms.The measured delay range exhibits excellent agreement with theoretical predictions derived from ODL waveguide parameters.This result addresses critical challenges in integrated photonic systems that require precise temporal control,particularly for applications in optical communications and quantum information processing,where a wide tuning range is paramount.
基金supported by the National Natural Science Foundation of China,No.82001604Guizhou Provincial Higher Education Science and Technology Innovation Team,No.[2023]072+1 种基金Guizhou Province Distinguished Young Scientific and Technological Talent Program,No.YQK[2023]040Guizhou Provincial Basic Research Program(Natural Science),No.ZK[2021]-368(all to LXiong),and Zunyi City Innovative Talent Team Training Plan,No.[2022]-2.
文摘Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.
基金The National Natural Science Foundation of China(No60671018,60121101)
文摘In order to assist the design of short interfering ribonucleic acids （siRNA）, 573 non-redundant siRNAs were collected from published literatures and the relationship between siRNAs sequences and RNA interference （RNAi） effect is analyzed by a support vector machine （SVM） based algorithm relied on a basebase correlation （BBC） feature. The results show that the proposed algorithm has the highest area under curve （AUC） value （0. 73） of the receive operating characteristic （ROC） curve and the greatest r value （0. 43） of the Pearson＇s correlation coefficient. This indicates that the proposed algorithm is better than the published algorithms on the collected datasets and that more attention should be paid to the base-base correlation information in future siRNA design.
文摘Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.
基金Supported by Tiantan Hospital Scientific Project Grant Fund
文摘AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line,BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1,pGPU6-2,pGPU6-3 and pGPU6-4,and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry,respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers.RESULTS:The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect,followed by pGPU6-2 and pGPU6-3 groups.Invasiveness and adhesion were more significantly reduced in pGPU6-1,pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However,no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups.CONCLUSION:RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line,BxPC-3,leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor.
文摘Hepatocellular carcinoma(HCC) is the 5th most common malignancy which is responsible for more than half million annual mortalities; also, it is the third leading cause of cancer related death. Unfavorablesystemic side-effects of chemotherapeutic agents and susceptibility to the degradation of small interfering RNAs(si RNAs), which can knock down a specific gene involved in the disease, have hampered their clinical application. So, it could be beneficial to develop an efficient carrier for the stabilization and specific delivery of drugs and si RNA to cells. Targeted nanoparticles have gained considerable attention as an efficient drug and gene delivery system, which is due to their capability in achieving the highest accumulation of cytotoxic agents in tumor tissue, modifiable drug pharmacokinetic- and bio-distribution, improved effectiveness of treatment, and limited sideeffects. Recent studies have shed more light on the advantages of novel drug loaded carrier systems vs free drugs. Most of the animal studies have reported improvement in treatment efficacy and survival rate using novel carrier systems. Targeted delivery may be achieved passively or actively. In passive targeting, no ligand as homing device is used, while targeting is achieved by incorporating the therapeutic agent into a macromolecule or nanoparticle that passively reaches the target organ. However, in active targeting, the therapeutic agent or carrier system is conjugated to a tissue or cell-specific receptor which is overexpressed in a special malignancy using a ligand called a homing device. This review covers a broad spectrum of targeted nanoparticles as therapeutic and nonviral si RNA delivery systems, which are developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and their characteristics and opportunities for the clinical applications of drugs and therapeutic si RNA are discussed in this article. Asialoglycoprotein receptors, low-density lipoprotein, ganglioside GM1 cell surface ligand, epidermal growth factor receptor receptors, monoclonal antibodies, retinoic acid receptors, integrin receptors targeted by Arg-Gly-Asp peptide, folate, and transferrin receptors are the most widely studied cell surface receptors which are used for the site specific delivery of drugs and si RNA-based therapeutics in HCC and discussed in detail in this article.
基金Supported by National Natural Science Foundation of China,No.81171660Zhejiang Provincial Natural Science Foundation of China,No.Y14C060003+4 种基金Natural Science Foundation of Ningbo,No.2012A610207The Scientific Innovation Team Project of Ningbo,No.2011B82014The Project of Key Disciplines in Ningbo,No.XKL11D2127 and No.XKL11D2128Foundation of Zhejiang Provincial Key Laboratory of Pathophysiology,No.201301K.C.Wong Magna Fund in Ningbo University
文摘Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expression of microRNAs(miRNAs)is significantly related to gastric cancer tumor stage,size,differentiation and metastasis.MiRNAs interrupt cellular signaling pathways,inhibit the activity of tumor suppressor genes,and affect the cell cycle in gastric cancer cells.Some miRNAs,including miR-21,miR-106a and miR-421,could be potential markers for the diagnosis of gastric cancer.Long non-coding RNAs (lncRNAs),a new research hotspot among cancerassociated ncRNAs,play important roles in epigenetic,transcriptional and post-transcriptional regulation.Several gastric cancer-associated lncRNAs,such as CCAT1,GACAT1,H19,and SUMO1P3,have been explored.In addition,Piwi-interacting RNAs,another type of small ncRNA that is recognized by gastroenterologists,are involved in gastric carcinogenesis,and piR-651/823represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice.Small interfering RNAs also function in posttranscriptional regulation in gastric cancer and might be useful in gastric cancer treatment.
基金supported by the National Natural Science Fund Project in China(grant No.:81060084)Jiangxi Provincial Natural Science Fund Project in China(grant No.:2010gzy0251)+1 种基金Jiangxi Provincial Health Department Project in China(grant No.:20131059)Jiangxi Provincial Department of Science and Technology Project in China(grant No.:20133BBG70071)
文摘Objective:To observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein rnRNA in the bone marrow,peripheral blood and nasal lavage fluid.Mctliods:Twenty-four BALB/c mice were randomly divided into the control group.PBS therapy group.siKNA therapy group and the CCR3 siRNA therapy group(n=6).Allergic rhinitis model were sensitized and stimulated by ovalbunfin,and CCR3 siKNA therapy group were administered with CCH3 transnasally before stimulated.The levels of the eosinophils CCR3.MBP.ECP and EPO in bone marrow,peripheral blood and nasal lavage fluid were detected by RT-PCR.Results:Compared to the control group and CCR3 siR.NA therapy group,the nasal mucosa of the PBS therapy group and siRNA therapy group developed epithalaxy.goblet cells hyperplasia,squamous epithelium metaplasia,epithelium necrosis,lamina propria and submucosa gland hyperplasia,vasodilatation,tissue edema,and the characterized eosinophil infiltration.RT-PCR indicated that the CCR3 rnRNA,MBP.ECP and EPC)expression in bone marrow,peripheral blood and nasal lavage fluid of the CCR3 siKNA therapy group was lower than the PBS therapy group and siR.NA therapy group(P<0.05).Conclusions:The RNA interference therapy to CCR3 by local administration pernasal can suppress the process of the development,migration and invasion of the allergic rhinitis eosinophil,thus can reduce the effect of eosinophils and then reduce the inflammation effect of the allergic rhinitis.It may be a new treatment for respiratory tract allergic inflammation.
基金Supported by Natural Science Foundation of Anhui Province,No. 090413098
文摘AIM:To investigate the expression of vascular endothelial cell growth factor (VEGF) and its receptors Fmslike tyrosine kinase 1 (FLT-1) and fetal liver kinase 1 (FLK-1) in colorectal carcinoma (CRC),and the blocking effects of small interfering RNAs (siRNAs) on VEGF expression in human colorectal cancer HCT116 cells.METHODS:Immunohistochemical staining for VEGF,FLT-1 and FLK-1 proteins was performed in 82 cases of CRC and 14 normal colorectal mucosae.A siRNA targeting VEGF was synthesized and transfected into HCT116 cells using lipofectamine 2000.Immunocytochemical staining and Western blotting analyses were performed to detect the expression of VEGF protein.The suppressive effect of the siRNA on cell proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltertrazolium bromide (MTT) assay.Cellular apoptosis was detected using flow cytometry (FCM).RESULTS:The expression of VEGF,FLT-1 and FLK-1 in tumor tissues was significantly higher than that in normal tissues (P=0.008,P=0.000,P=0.000).The expression of VEGF was positively correlated with both lymph node metastasis and clinical stage (P=0.009 and P=0.025,respectively).Immunocytochemistry showed that the expression of VEGF was weakly positive and Western blotting indicated a significant reduction in VEGF-siRNA cell protein levels.VEGF-siRNA cell growth inhibition was assessed by the MTT assay,and the tumor cell proliferation rate was significantly different at 24,48,and 72 h after transfection.FCM results showed that the VEGF-siRNA group had an apparent aneuploid peak.CONCLUSION:VEGF,FLT-1 and FLK-1 are associated with colorectal carcinogenesis.siRNA silencing of the VEGF gene suppresses proliferation,and induces apoptosis in HCT116 cells.The results suggest that VEGF may be a new gene therapy target for colorectal cancer.
基金the financial support from the National Natural Science Foundation of China (Grant No.81373335)Liaoning Province Natural Science Foundation (Grant No.20170541025)
文摘RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, providing a potentially effective platform for the treatment of a wide array of diseases. However, similar to other nucleic acid-based drugs,the major hurdle of RNAi therapy is lack of efficient and non-immunogenic delivery vehicles. Currently, viruses, synthetic polymers, and lipid-based carriers are among the most widely studied vehicles for small RNA delivery. However, many drawbacks are reported to be associated with these delivery vehicles. There is a pressing need to replace them with more efficient and better-tolerated approaches. Exosomes secreted from the endocytic compartment of live cells, are a subtype of endogenous extracellular vesicles that transfer genetic and biochemical information among different cells, thus playing an important role in cellcell communication. Recently, accumulating attention has been focused on harnessing exosomes as nanaocarriers for small RNAs delivery. Due to their natural role in shuttling endogenous nucleic acid in our body, exosomes may exhibit higher delivery efficiency, lower immunogenicity, and better compatibility than existing foreign RNA carriers. Importantly,exosomes own intrinsic homing capacity that can guide small RNAs across natural membranous barriers. Moreover, such a capacity can be further improved by adding appropriate targeting moieties. In this manuscript, we briefly review the progress and challenges of RNAi therapy, and discuss the potential of exosomes' applications in small RNA delivery with focus on the most recent advances in exosome-based small RNA delivery for disease therapy.
基金supported by the Grant No.2003AA208215 from the National High Technology Programs of Chinathe Grant No.30270311 from the National Natural Science Foundation of China.
文摘RNA interference (RNAi) is triggered by the presence of a double-stranded RNA (dsRNA), and results in the silencing of homologous gene expression through the specific degradation of an mRNA containing the same sequence. dsRNAmediated RNAi can be used in a wide variety of eucaryotes to induce the sequence-specific inhibition of gene expression.Synthetic 21-23 nucleotide (nt) small interfering RNA (siRNA) with 2 nt 3' overhangs was recently found to mediate efficient sequence-specific mRNA degradation in mammalian cells. Here, we studied the effects of synthetic siRNA duplexes targeted to SARS coronavirus structural proteins E, M, and N in a cell culture system. Among total 26 siRNA duplexes, we obtained 3 siRNA duplexes which could sequence-specifically reduce target genes expression over 80％ at the concentration of 60 nM in Vero E6 cells. The downregulation effect was in correlation with the concentrations of the siRNA duplexes in a range of 0～60 nM. Our results also showed that many inactive siRNA duplexes may be brought to life simply by unpairing the 5' end of the antisense strands. Results suggest that siRNA is capable of inhibiting SARS coronavirus genes expression and thus may be a new therapeutic strategy for treatment of SARS.
基金Supported by Science and Technology Project of Hunan Province, China, No. 2013FJ3151
文摘AIM: To further analyse cancer involvement of basic transcription factor 3 (BTF3) after detection of its upregulation in gastric tumor samples. METHODS: BTF3 transcription rates in human gastric tumor tissue samples (n = 20) and adjacent normal tissue (n = 18) specimens as well as in the gastric cancer cell lines AGS, SGC-7901, MKN-28, MKN-45 and MGC803 were analyzed via quantitative real-time polymerase chain reaction. The effect of stable BTF3 silencing via infection with a small interfering RNA (siRNA)-BTF3 expressing lentivirus on SGC-7901 cells was measured via Western blotting analysis, proliferation assays, cell cycle and apoptosis profiling by flow cytometry as well as colony forming assays with a Cellomic Assay System. RESULTS: A significant higher expression of BTF3 mRNA was detected in tumors compared to normal gastric tissues (P < 0.01), especially in section tissues from female patients compared to male patients, and all tested gastric cancer cell lines expressed high levels of BTF3. From days 1 to 5, the relative proliferation rates of stable BTF3-siRNA transfected SGC7901 cells were 82%, 70%, 57%, 49% and 44% compared to the control, while the percentage of cells arrested in the G 1 phase was significantly decreased (P = 0.000) and the percentages of cells in the S (P = 0.031) and G 2 /M (P = 0.027) phases were significantly increased. In addition, the colony forming tendency was significantly decreased (P = 0.014) and the apoptosis rate increased from 5.73% to 8.59% (P = 0.014) after BTF3 was silenced in SGC7901 cells. CONCLUSION: BTF3 expression is associated with enhanced cell proliferation, reduced cell cycle regulation and apoptosis and its silencing decreased colony forming and proliferation of gastric cancer cells.
基金Supported by A grant of the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A092258)FG08-11-06 of the 21C Frontier Functional Human Genome Project from the Ministry of Education, Science and Technology
文摘AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.
基金Supported by The Innovation Fund of Central South University,No.234077231
文摘AIM:To investigate the function of gamma-aminobutyric acid(GABA)and gamma-aminobutyric acid A receptorθsubunit(GABRQ)in hepatocellular carcinoma(HCC).METHODS:Semiquantitative polymerase chain reaction was used for detecting the expression of GABRQ receptor among HCC cell line HepG2,normal liver cell line L-02,non-malignant Chang's liver cells,8 samples of HCC tissues and paired non-cancerous tissues.HepG2 cells were treated with GABA at serial concentrations(0,1,10,20,40 and 60μmol/L),and their proliferating abilities were analyzed with the methyl thiazolyl tetrazolium assay,cell cycle analysis and tumor implanted in nude mice.Small interfering RNA was used for knocking down the endogenous GABRQ in HepG2.Proliferating abilities of these cells treated with or without GABA were analyzed.RESULTS:We identified the overexpression of GABRQ in HCC cell lines and half of the tested HCC tissues.Knockdown of endogenous GABRQ expression in HepG2 attenuated HCC cell growth,suggesting its role in HCC cell viability.We studied the effect of GABA in the proliferation of GABRQ-positive cell lines in vitro and in vivo,and found that GABA increased HCC growth in a dosedependent manner.Notably,the addition of GABA into the cell culture medium promoted the proliferation of GABRQ-expressing HepG2 cells,but not GABRQ-knockdown HepG2 cells,which means that GABA stimulates HepG2 cell growth through GABRQ.CONCLUSION:GABRQ play important roles in HCC development and progression and could be a promising molecular target for the development of new diagnostic and therapeutic strategies of HCC.
