The Role And Mechanism Of Long Non-coding RNA LINC00152 And Lnc-Tim3 In The Occurrence And Development Of Hepatocellular Carcinoma

Hepatocellular carcinoma(HCC)is well known as the sixth most common malignant tumor and the third leading cause of cancer-related deaths globally.LINC00152 was documented as an important long non-coding RNA(LncRNA)involved in the pathogenesis of gastric cancer;however,the detailed mechanism of action of LINC00152 remains unknown.Here,based on the increased level of LINC00152 in HCC tissues,we found that LINC00152 could promote cell proliferation in vitro and tumor growth in vivo.Furthermore,microarray-based analysis indicated that LINC00152 could activate the mechanistic target of rapamycin(mTOR)pathway by binding to the promoter of EpCAM through a cis-regulation.Thus,LINC00152 might be involved in the oncogenesis of HCC by activating the mTOR signaling pathway and might be a novel index for clinical diagnosis and treatment of HCC in the future.Although one of the first comprehensive examinations of long noncoding RNA(IncRNA)expression was performed in human CD8+T lymphocyte cells,little is known about their roles in CD8+T cells functions during the progression of hepatocellular carcinoma(HCC).Here,we show that Lnc-Tim3 is upregulated and negatively correlates with IFN-y and IL-2 producing in tumor-infiltrating CD8+T cells of HCC patients.Lnc-Tim3 plays a pivotal role in stimulating CD8+T exhaustion and the survival of the exhausted CD8+T cells.Mechanistically,Lnc-Tim3 specifically binds to Tim-3 and blocks its interaction with Bat3,thus suppressing downstream Lck/NFAT1/AP-1 signaling and IFN-y/IL-2 production,leading to CD8+T cells activity weakening.Meanwhile,the Bat3 relocation to cell nucleus will enhance p300-dependent p53 and RelA transcriptional activation of anti-apoptosis genes including MDM2 and Bcl-2.Therefore,Lnc-Tim3 exerts an inhibitory effect on antitumor immunity via promoting CD8+T cell exhausted,thereby providing a potential therapeutic target for HCC.