Many circular RNAs(circRNAs)are reported to be abnormally expressed during the progression of various tumors,and these circRNAs can be used as anti-tumor targets.Therefore,it is important to identify circRNAs that can...Many circular RNAs(circRNAs)are reported to be abnormally expressed during the progression of various tumors,and these circRNAs can be used as anti-tumor targets.Therefore,it is important to identify circRNAs that can be used effectively for the clinical diagnosis and treatment of colorectal cancer(CRC).Here,we report that hsa_Circ_0000826(Circ_0000826),a circ RNA with significantly reduced expression level in CRC tissues,is associated with a poor prognosis in patients.The silencing of Circ_0000826 promotes the proliferation of CRC cells.Conversely,the overexpression of Circ_0000826 restricted CRC cell proliferation both in vitro and in vivo.Furthermore,Circ_0000826 could target AU-rich element RNA-binding protein 1(AUF1).AUF1,known as heterogeneous nuclear ribonucleoprotein D(hnRNP D),could bind to the c-MYC 3’-UTR and promote c-MYC expression.When Circ_0000826 binds to AUF1,it competitively inhibits the binding of AUF1 to the c-MYC 3’-UTR,which inhibits the c-MYC expression and cell proliferation.These results provide novel insights into the functional mechanism of Circ_0000826 action in CRC progression and indicate its potential use as a therapeutic target in CRC.展开更多
AIM:To investigate the impact of hsa_circ_0007482 on the proliferation and apoptosis of human pterygium fibroblasts(HPFs)and its correlation with the severity grades of pterygium.METHODS:Pterygium and normal conjuncti...AIM:To investigate the impact of hsa_circ_0007482 on the proliferation and apoptosis of human pterygium fibroblasts(HPFs)and its correlation with the severity grades of pterygium.METHODS:Pterygium and normal conjunctival tissues were collected from the superior area of the same patient’s eye(n=33).The correlation between pterygium severity and hsa_circ_0007482 expression using quantitative reversetranscription polymerase chain reaction(RT-qPCR)were analyzed.Three distinct siRNA sequences targeting hsa_circ_0007482,along with a negative control sequence,were transfected into HPFs.Cell proliferation was assessed using the cell counting kit-8.Expression levels of Ki67,proliferating cell nuclear antigen(PCNA),Cyclin D1,Bax,B-cell lymphoma-2(Bcl-2),and Caspase-3 were measured via RT-qPCR.Immunofluorescence staining was employed to detect Ki67 and vimentin expressions.Apoptosis was evaluated using flow cytometry.RESULTS:Hsa_circ_0007482 expression was significantly higher in pterygium tissues compared to normal conjunctival tissues(P<0.001).Positive correlations were observed between hsa_circ_0007482 expression and pterygium severity,thickness,and vascular density.Knockdown of hsa_circ_0007482 inhibited cell proliferation,reducing the mRNA expression of Ki67,PCNA,and Cyclin D1 in HPFs.Hsa_circ_0007482 knockdown induced apoptosis,increasing mRNA expression levels of Bax and Caspase-3,while decreasing Bcl-2 expression in HPFs.Additionally,hsa_circ_0007482 knockdown attenuated vimentin expression in HPFs.CONCLUSION:The downregulation of hsa_circ_0007482 effectively hampers cell proliferation and triggers apoptosis in HPFs.There are discernible positive correlations detected between the expression of hsa_circ_0007482 and the severity of pterygium.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81802470,31800658,and U1804173)the Department of Science and Technology,Henan Province(Grant Nos.212102310621 and 192102310362)+1 种基金Joint construction project of Henan Medical Science and technology research plan(No.LHGJ20210910)the Xinxiang Medical University research funding(Grant No.XYBSKYZZ201632)。
文摘Many circular RNAs(circRNAs)are reported to be abnormally expressed during the progression of various tumors,and these circRNAs can be used as anti-tumor targets.Therefore,it is important to identify circRNAs that can be used effectively for the clinical diagnosis and treatment of colorectal cancer(CRC).Here,we report that hsa_Circ_0000826(Circ_0000826),a circ RNA with significantly reduced expression level in CRC tissues,is associated with a poor prognosis in patients.The silencing of Circ_0000826 promotes the proliferation of CRC cells.Conversely,the overexpression of Circ_0000826 restricted CRC cell proliferation both in vitro and in vivo.Furthermore,Circ_0000826 could target AU-rich element RNA-binding protein 1(AUF1).AUF1,known as heterogeneous nuclear ribonucleoprotein D(hnRNP D),could bind to the c-MYC 3’-UTR and promote c-MYC expression.When Circ_0000826 binds to AUF1,it competitively inhibits the binding of AUF1 to the c-MYC 3’-UTR,which inhibits the c-MYC expression and cell proliferation.These results provide novel insights into the functional mechanism of Circ_0000826 action in CRC progression and indicate its potential use as a therapeutic target in CRC.
文摘目的:子宫内膜癌是女性生殖系统常见的恶性肿瘤,以子宫内膜样癌(endometrioid adenocarcinoma,EEC)最常见,其发病机制目前尚不清楚,已有研究证明环状RNA(circular RNA,circRNA)的表达与EEC的进展有关。本研究旨在检测hsa_circ_0007067在EEC中的表达,并探讨Hsa_circ_0007067与EEC临床病理特征的关系。方法:应用高通量测序分析2例EEC组织和2例正常子宫内膜组织基因表达水平,以|log2(Fold changes)|≥1.5且P<0.05为筛选标准,选择下调最显著的hsa_circ_0007067为研究对象,应用实时聚合酶链反应(real-time PCR)检测36例EEC组织(EEC组)和36例正常子宫内膜组织(对照组)中hsa_circ_0007067的相对表达量。生物信息学分析预测hsa_circ_0007067的结合位点和编码能力。结果:EEC组中hsa_circ_0007067表达水平显著低于对照组(P<0.05),且表达水平与国际妇产科联盟(Inter-national Federation of Gynecology and Obstetrics,FIGO)分期和组织分化程度有关;受试者操作特征(receiver operating characteristic,ROC)曲线显示曲线下面积(area under curve,AUC)为0.936,敏感度为0.833,特异度为0.889,最佳截断值为0.722,差异具有统计学意义(P<0.05)。Hsa_circ_0007067具有翻译成多肽的潜能,circbank数据库预测其miRNA潜在结合位点共24个。结论:Hsa_circ_0007067与EEC的发生、发展相关,可能通过与下游靶基因miRNA结合或编码蛋白质功能影响EEC的进程,有望作为EEC早期筛查和判断预后的分子指标。
基金Supported by Guangdong Basic and Applied Basic Research Foundation (No.2021A1515111012).
文摘AIM:To investigate the impact of hsa_circ_0007482 on the proliferation and apoptosis of human pterygium fibroblasts(HPFs)and its correlation with the severity grades of pterygium.METHODS:Pterygium and normal conjunctival tissues were collected from the superior area of the same patient’s eye(n=33).The correlation between pterygium severity and hsa_circ_0007482 expression using quantitative reversetranscription polymerase chain reaction(RT-qPCR)were analyzed.Three distinct siRNA sequences targeting hsa_circ_0007482,along with a negative control sequence,were transfected into HPFs.Cell proliferation was assessed using the cell counting kit-8.Expression levels of Ki67,proliferating cell nuclear antigen(PCNA),Cyclin D1,Bax,B-cell lymphoma-2(Bcl-2),and Caspase-3 were measured via RT-qPCR.Immunofluorescence staining was employed to detect Ki67 and vimentin expressions.Apoptosis was evaluated using flow cytometry.RESULTS:Hsa_circ_0007482 expression was significantly higher in pterygium tissues compared to normal conjunctival tissues(P<0.001).Positive correlations were observed between hsa_circ_0007482 expression and pterygium severity,thickness,and vascular density.Knockdown of hsa_circ_0007482 inhibited cell proliferation,reducing the mRNA expression of Ki67,PCNA,and Cyclin D1 in HPFs.Hsa_circ_0007482 knockdown induced apoptosis,increasing mRNA expression levels of Bax and Caspase-3,while decreasing Bcl-2 expression in HPFs.Additionally,hsa_circ_0007482 knockdown attenuated vimentin expression in HPFs.CONCLUSION:The downregulation of hsa_circ_0007482 effectively hampers cell proliferation and triggers apoptosis in HPFs.There are discernible positive correlations detected between the expression of hsa_circ_0007482 and the severity of pterygium.
