Upregulation Of MiR-124-3p By Long Non-coding RNA H19 And Liver X Receptor Suppresses The Growth Of HCC Cells

Background:The morbidity and mortality of hepatocellular carcinoma all over the world are in front of another malignant tumor,and which in China is located in the first in the Asia.Now the therapy of HCC is surgical resection assisted with chemotherapy and radiotherapy,but it has poor outcome.In recent years,the research about application of mi RNA in cancer treatment has been drawing so many attention.Among them mi R-124-3p is a tumor suppressor which is closely related to the proliferation,migration and invasion of cancer,and mi R-124-3p has lower expression in cancer tissues compared with corresponding adjacent tissues.mi R-124-3p inhibits the growth of HCC through down-regulating the expression of cyclin D1,however,the report about the regulation of itself is scare.Liver X receptor(LXR),which participates in glucolipid metabolism and anti-inflammatory response,is a sort of transcription factors.Anti-tumor which is a new feature of LXR arises attention to it yearly,but the mechanism of it has not been completely elucidated.H19 is a kind of non-coding RNA whose effect about tumor-promoting or tumor-inhibiting is controversial.Previous reports have shown that H19 expresses lowly in liver tumor and hepatocellular carcinoma and can suppress the migration and invasion of HCC.mi R-124-3p,LXR and H19,all of them have the function in anti-tumor,but the correlation between H19 and mi R-124-3p or LXR and mi R-124-3p is by far not clear.Objective:To investigate the correlation between H19 and mi R-124-3p and LXR and mi R-124-3p in HCC,and the effect of H19 and LXR on the growth of HCC.Methods:(1)A recombinant plasmid overexpressing H19(pc DNA3.1-H19)was constructed and was separately transfected into Hep G2 and SMMC7721 cells in the presence or absence of antigomi R-124-3p,then the growth of the cells,the expression of mi R-124-3p and cyclin D1 were examined by CCK-8 assay,QRT-PCR and Western blot respectively.(2)After being treated with GW3965 and TO901317 in the presence or absence of antigomi R-124-3p,the growth of the Hep G2 cells,and the expression of mi R-124-3p and cyclin D1 were measured by CCK-8 assay,QRT-PCR and Western blot respectively.(3)A total of 3.1×106 Hep G2 cells in 100μL phosphate-buffered saline were subcutaneously injected into theaxilla of each nude mouse,when tumor is palpable(about 8 days),the mice were randomly assigned to control and test groups(n = 6 per group),a daily intraperitoneal injection of GW3965(30mg/kg/d)or vehicle were given to the mice.After 7 days,the mice were sacrificed,and the tumors were harvested for analysis of the expression of mi R-124-3p and cyclin D1.Result:1.Overexpression of H19 in Hep G2 and SMMC7721 cellsleads to the upregulation of mi R-124-3p,inhibition of thecyclin D1,and suppression of growth.2.LXR agonists can inhibit Hep G2 cells’ growth in a dose-dependent manner through enhancing the expression of mi R-124-3p.3.In vivo experiment,GW3965 has the same effects as in vitro.Conclusion:1.lnc RNA H19 can suppress the growth of HCC through facilitating the expression of mi R-124-3p and repressing cyclin D1.2.LXR agonists lead to the overexpression of mi R-124-3p and the suppression of cyclin D1,then can inhibit Hep G2 cells’ growth.