LINC00862通过RBM47介导的正反馈环路抑制肝癌进展的分子机制

肝细胞肝癌（HCC）是全球最常见的致死性癌症之一，其发生发展的机制仍未完全阐明；目前已知长链非编码RNA（lncRNA）与HCC发生发展有关。申请人前期发现某一功能未知的lncRNA-LINC00862在HCC组织中低表达且与临床预后相关，体内外预实验也同时证实LINC00862可以显著抑制HCC进展。进一步研究发现：LINC00862与抑癌基因RBM47表达相关且彼此之间存在正向调控，而后者本身即可通过多条通路抑制肝癌进展。据此，我们推测LINC00862可能通过RBM47介导的正反馈环路发挥抑癌作用，而其中深入的分子机制并不清楚。本课题将立足于LINC00862对肝癌的抑制作用，利用DNA、RNA及蛋白质互作调控深入探讨其具体分子机制。这将丰富我们对lncRNA在肝癌调控方面及相关分子机制的认知，也为肝癌治疗寻找新的靶点。

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer associated death worldwide, of which the etiology and pathogenesis remain incompletely clarified. A wide array of researches indicated that long chain non-coding RNA (lncRNA) plays key roles in pathogenesis and progression of HCC. The applicant discovered a certain lncRNA with unknown function, namely LINC00862, which was downregulated in HCC tissue and was associated with clinical prognosis of patients. Pre-experiments have verified that LINC00862 significantly suppressed the development of HCC in vitro and in vivo. Furthermore, LINC00862 was verified to be related to the expression of tumor suppressor RBM47 and they could actually positively regulate each other. Meanwhile, RBM47 can inhibit the progression of HCC through multiple signaling pathways. According to the aforementioned evidence, we speculate that LINC00862 may inhibit the progression of HCC through a positive feedback loop mediated by RBM47, but the underlying molecular mechanism is unrevealed. The present project is launched around the effects of LINC00862 on tumor suppression to further investigate the underlying molecular mechanism at the aspects of DNA, RNA and protein regulation. This research will enrich our current understanding regarding the functions and molecular mechanisms of lncRNA in HCC, and provide potential novel targets for HCC treatment.