RNA甲基化m6A修饰介导的pri-miRNA加工成熟在前列腺癌中作用及分子机制研究

前列腺癌严重危害老年男性健康，但其发生发展机制仍不清楚。miRNA参与了前列腺癌进展，但对于这些miRNAs的生成机制尚不十分明确。我们前期研究发现与pri-miRNA加工成熟相关的RNA甲基化m6A相关基因METTL3、HNRNPA2B1在前列腺癌中均明显高表达并且与预后相关，敲低两基因后均明显抑制其增殖与转移。miRNA测序结果提示敲低METTL3或HNRNPA2B1后共31个共有miRNA表达受到抑制，由此推断m6A很可能参与pri-miRNA的加工成熟。据此，本项目组拟利用临床样本进一步研究上述基因表达模式及其临床价值；通过MeRIP、RIP以及CLIP等技术进一步明确METTL3/HNRNPA2B1介导pri-miRNA加工成熟中的分子机制；阐明受m6A调控miRNA的生物学功能、作用机制，并利用RISH检测技术在前列腺癌临床样本中进行miRNA检测，鉴定其临床价值。

Prostate cancer seriously harms the health of elderly men, but the mechanism of the carcinogenesis and progression is still unclear. MiRNAs are involved in prostate cancer progression, but the mechanism by which these miRNAs are generated is elusive. Our previous finding revealed that the pri-miRNA processing-related RNA methylation m6A genes METTL3 and HNRNPA2B1 were significantly overexpressed in prostate cancer and associated with prognosis. Depletion of both genes significantly inhibited tumor proliferation and metastasis. The further miRNA sequencing result suggested that expression of 31 common miRNAs was suppressed after knocking down METTL3 or HNRNPA2B1, and it was concluded that m6A is likely to be involved in the pri-miRNA processing. Based on this, we intend to use clinical samples to further investigate the above gene expression pattern and its clinical value; To further clarify the molecular mechanism of pri-miRNA processing mediated by METTL3/HNRNPA2B1 through technologies such as MeRIP, RIP and CLIP; To investigate the biological function and mechanism of m6A-induced miRNAs, and to identify its clinical value by detecting these miRNAs in clinical prostate cancer samples using RISH staining technology.