m6A/LncRNA LHX1-DT/PDCD4途径调控肾透明细胞癌增殖和转移作用机制研究

LncRNA LHX1-DT调控肾透明细胞癌增殖和转移作用机制不清楚。课题组发现肾透明细胞癌中LHX1-DT表达水平和m6A水平均降低；预测发现LHX1-DT存在m6A修饰位点，LHX1-DT和PDCD4存在相同的miR-590-5p结合位点；LHX1-DT过表达抑制miR-590-5p表达，促进PDCD4表达，抑制肾透明细胞癌增殖和侵袭；抑制去甲基化酶FTO后LHX1-DT m6A修饰及表达增加；m6A结合蛋白IGF2BP2与LHX1-DT结合，IGF2BP2沉默抑制LHX1-DT表达。那么m6A是否可通过调控LHX1-DT表达以及通过ceRNA机制介导肾透明细胞癌增殖和转移？本课题拟明确m6A调控LHX1-DT表达作用及机制，阐明LHX1-DT通过ceRNA机制参与miR-590-5p调控PDCD4介导肾透明细胞癌增殖和转移的机制，为发现逆转肾透明细胞癌增殖和转移的新靶点奠定基础。

The mechanism of lncRNA LHX1-DT regulated proliferation and metastasis of ccRCC is unclear. We discovered that the expression levels of LHX1-DT and m6A modification were both decreased in ccRCC. m6A modification sites were predicted on LHX1-DT through bioinformatic software. We also found that LHX1-DT and PDCD4 had the same miR-590-5p binding sites. Overexpression of LHX1-DT could promote PDCD4 expression to inhibit proliferation and metastasis of ccRCC through downregulation of miR-590-5p. The expression of LHX1-DT and m6A modification increased after inhibition of demethylase FTO. m6A binding protein, IGF2BP2, could combine with LHX1-DT, and silencing of IGF2BP2 could suppress LHX1-DT expression. We want to know whether m6A can regulate the expression of LHX1-DT and mediate proliferation and metastasis of ccRCC through ceRNA mechanism. The purpose of this study is to clarify the mechanism of m6A in regulating the expression of LHX1-DT. We also hope to elucidate the way by which LHX1-DT participates in miR-590-5p regulation of PDCD4 mediated proliferation and metastasis of ccRCC. Our study could lay a foundation for finding new targets to reverse proliferation and metastasis of ccRCC.