摘要
目的探讨hsa-circTP63对胃癌细胞增殖、侵袭、迁移和上皮-间质转化(epithelial-mesenchymal transitions,EMT)的影响,以及其对miR-873-3p的调控机制。方法分别以hsa-circTP63-NC、hsa-circTP63-mimic、hsa-circTP63-inhibitor、hsa-circTP63-NC+miR-873-3p-agomir-NC、hsa-circTP63-mimic+miR-873-3p-agomir转染胃癌细胞MGC-823。EDU检测各组细胞的增殖,Transwell小室检测各组细胞的侵袭和迁移能力;Western blotting检测各组细胞Ⅱ型跨膜丝氨酸蛋白酶4(typeⅡtransmembrane protease serine 4,TMPRSS4)、E-cadherin和Vimentin的表达;双荧光素酶实验检测hsa-circTP63、miR-873-3p、TMPRSS4三者的关系。结果在胃癌细胞中,上调hsa-circTP63的表达,细胞的增殖、侵袭、迁移性能增强,TMPRSS4和Vimentin的表达升高,E-cadherin的表达降低,推动EMT过程;下调hsa-circTP63的表达,细胞的增殖、侵袭、迁移性能减弱,TMPRSS4和Vimentin的表达降低,E-cadherin的表达升高,抑制EMT过程;miR-873-3p-agomir可部分逆转hsa-circTP63-mimic对细胞表型的影响;双荧光素酶实验结果显示hsa-circTP63靶向miR-873-3p调控TMPRSS4的表达。结论hsa-circTP63在胃癌细胞中呈高表达,可通过调控miR-873-3p/TMPRSS4的表达影响胃癌细胞的增殖、侵袭和迁移。
Objective To investigate the effect of hsa-circTP63 on gastric cancer cell proliferation,invasion,migration and epithelial-mesenchymal transitions(EMT),and its regulation mechanism on miR-873-3p.Methods Hsa-circ-TP63NC,hsa-circTP63-mimic,hsa-circTP63-inhibitor,hsa-circTP63-NC+miR-873-3p-agomir-NC,hsa-circTP63-mimic+miR-873-3p-agomir were transfected into gastric cancer cell MGC-823.EDU was used to detect the proliferation activity of each group of cells,the Transwell chamber was used to detect the invasion and metastasis ability of each group of cells.Western blotting was used to detect the expression levels of typeⅡtransmembrane protease serine 4(TMPRSS4),E-cadherin and Vimentin.Dual luciferase assay was used to detect the relationship between hsa-circTP63,miR-873-3p and TMPRSS4.Results In gastric cancer cells,the expressions of hsa-circTP63 increased,the cell proliferation ability,invasion ability and metastasis ability were enhanced,the expressions of TMPRSS4 and Vimentin were increased,and the expression of E-cadherin was decreased,which promoted the EMT process;down-regulated the expression of hsa-circTP63,the cell proliferation ability,invasion ability and metastasis ability were weakened,the expressions of TMPRSS4 and Vimentin were reduced,the expression of E-cadherin was increased,and EMT process was inhibited;miR-873-3p-agomir could partially reverse the effect of hsa-circTP63-mimic on cell phenotype.The results of dual luciferase experiments showed that hsa-circTP63 targets miR-873-3p to regulate the expression of TMPRSS4.Conclusion Hsa-circTP63 is highly expressed in gastric cancer cells,which can affect the proliferation,invasion and migration of gastric cancer cells by regulating the expression of miR-873-3p/TMPRSS4.
作者
王士铭
罗未名
王开升
宋其隆
王飞通
WANG Shiming;LUO Weiming;WANG Kaisheng;SONG Qilong;WANG Feitong(Department of Hepatobiliary Surgery,Affiliated Hospital of Xuzhou Medical University,Xuzhou 221000,China)
出处
《胃肠病学和肝病学杂志》
2025年第7期1006-1012,共7页
Chinese Journal of Gastroenterology and Hepatology