硬度激活的lncRNA PSMA3-AS1靶向miR-378a-3p/ZFP36L2促进肝癌细胞增殖OA

Objective To elucidate the effects of long non-coding RNA(lncRNA)proteasome 20S subunit alpha 3 antisense RNA 1(PSMA3-AS1)and its direct downstream miR-378a-3p/zinc finger protein 36 ring finger protein like 2(ZFP36L2)on the proliferation of liver cancer cells and its molecular mechanism.Methods A total of 30 samples of hepatocellular carcinoma tissues and their adjacent non-cancerous tissues were obtained from patients who underwent hepatectomy at the First Affiliated Hospital of Xi'an Jiaotong University between January 1st,2020,and December 1st,2023.The levels of lncRNA PSMA3-AS1,miR-378a-3p,and ZFP36L2 were detected by qRT-PCR in liver cancer tissues as a high-stiffness environment relative to adjacent tissues.The expression of lncRNA PSMA3-AS1 in human hepatoblastoma cell line Hep-G2 and human hepatocellular carcinoma cell line SK-Hep-1 induced by matrix stiffness was detected by qRT-PCR.The expressions of lncRNA PSMA3-AS1,miR-378a-3p,and ZFP36L2 were either inhibited or overexpressed in SK-Hep-1 and Hep-G2 cells by using small interfering RNA,overexpression vectors,and oligonucleotide mimics.Cell proliferation was detected by cell counting kit-8(CCK-8)assay.Dual luciferase reporting assay was used to detect the targeting relationship between lncRNA PSMA3-AS1 and miR-378a-3p and between miR-378a-3p and ZFP36L2.Western blot was used to detect the expression of ZFP36L2.Results qRT-PCR results showed that SK-Hep-1 and Hep-G2 cells had higher lncRNA PSMA3-AS1 and lower miR-378a-3p expressions with high environmental stiffness of 25.6 kPa than those with low environmental stiffness of 0.4 kPa(all P<0.05).Compared with normal liver tissues,the expression of lncRNA PSMA3-AS1 in liver cancer tissues was increased,while the expression of miR-378a-3p was decreased(both P<0.05).The overexpression of lncRNA PSMA3-AS1,inhibition of miR-378a-3p,and overexpression of ZFP36L2 in Hep-G2 cells all significantly enhanced cell proliferation(all P<0.05).In SK-Hep-1 cells,The inhibition of lncRNA PSMA3-AS1,overexpression of miR-378a-3p,and inhibition of ZFP36L2 all significantly reduced cell proliferation(all P<0.05).Dual luciferase report-ing assay showed that lncRNA PSMA3-AS1 targeted miR-378a-3p,and miR-378a-3p targeted ZFP36L2.Conclusions Interfering the expression of lncRNA PSMA3-AS1 can reduce the proliferation of liver cancer cells through miR-378a-3p/ZFP36L2,which may become a new therapeutic target of liver cancer.