The Molecular Mechanism Of Long Noncoding RNA TMEM75 In The Progression Of Hepatocellular Carcinoma

Many long noncoding RNAs that play an important role in the progression of cancer have been found.The molecular mechanisms involved in it are also diverse.And it is necessary to understand the specific molecular mechanisms involved in the progression of cancer for the treatment of cancer.This study investigated the biological function of a novel lncRNA-TMEM75 in the progression of hepatocellular carcinoma and tried to reveal the molecular mechanisms involved in the progression of hepatocellular carcinoma.Methods:Quantitative Real-time PCR was used to detect the expression of TMEM75 in tumor and normal tissues of HCC patients.Trypan blue staining cell counting experiment,scratch healing experiment,and transwell experiment were used to detect cell proliferation,migration,and invasion,respectively.The xenograft model of nude mice was used to simulate the effect of TMEM75 on tumor growth in vivo.ChIP assay was used to investigate the effect of TMEM75 on histone modifications in PVT1's promoter region.RIP and RNA pulldown experiments were used to detect the interaction of TMEM75 with MLL1 and WDR5.Gene expression profiling microarray analysis was used to find downstream genes that are jointly regulated by PVT1 and TMEM75.Results:We found the expression of TMEM75 in the tumor tissues of HCC patients was higher than normal tissues,suggesting that it may be an oncogene in HCC.Subsequently,we also found that TMEM75 can affect cell proliferation by affecting the cell cycle of HCC cells,and it also promotes the invasion ability of HCC cells.The xenograft model of nude mice also shows that TMEM75 promotes tumor growth in vivo.In order to clarify its molecular mechanisms that promote the progression of HCC,we used a series of molecular biology experiments to find that TMEM75 can recruit MLL1 and WDR5 to the promoter region of PVT1,and thus promote the methylation of histone H3K4 near the PVT1 's promoter region.And that upregulates the expression of PVT1.Finally,we found a downstream gene OGFR that is jointly regulated by TMEM75 and PVT 1.TMEM75 and PVT1 can promote the proliferation and invasion of HCC cells by downregulating the expression of OGFR.In summary,we have found that a TMEM75-PVT1-OGFR regulatory axis plays an important role in the progression of HCC.