METTL3 promotes prostate cancer progression by regulating miR‐182 maturation in m6A‐dependent manner

METTL3 was known to run through the whole cycle of RNA. It relied on m6A modification in the mRNAs of cancer-related genes to regulate tumour progression. The development of prostate cancer cells could be promoted by METTL3 via hedgehog pathway. Recent studies had shown that the effect of METTL3 on non-coding RNA was mainly dependent on the modification of m6A. However, it is still unknown whether METTL3 promotes tumour development through this mechanism in prostate cancer. The expression of METTL3 in prostate cancer tissues and cells was analysed by qRT-PCR and Western blot assays. CCK-8 assay, colony formation assay, wound-healing assay and transwell assays were conducted to detect the impact of METTL3 on cell proliferation, migration and invasion. Nude mice tumour models were built to evaluate the role of METTL3 in tumorigenesis. N6-methyladenosine (m6A) RNA immunoprecipitation assay (MeRIP) and co-immunoprecipitations assays were performed to verified that METTL3 upregulated the m6A level, interacted with microprocessor protein DGCR8, recognized the m6A modification of pre-miR-182 to regulate its maturation.METTL3 was highly expressed in prostate cancer, and knockdown of METTL3 significantly inhibited cell proliferation, migration, invasion and tumorigenesis, while overexpression of METTL3 promoted cell proliferation, migration, invasion and tumorigenesis in PCa. In addition, we found that METTL3 upregulating the level of m6A, and interacted with DGCR8 to recognize the m6A modification of pre-miR-182 to regulate its splicing and maturation and promote the high expression of miRNA. Our study suggests that METTL3 could be used in targeted therapies for PCa.