Systematic Investigation Of Mrna N-6-Methyladenosine Machinery In Primary Prostate Cancer

Background. Appreciable findings have pointed out pivotal roles of N-6-methyladenosine (m(6)A) machinery in cancer onset and progression. However, limited efforts have been directed towards relevant research in the prostate cancer area. Methods. A PubMed search was conducted to acquire components of the mRNA m(6)A machinery. Multiomics integration was performed to systematically investigate the mRNA m(6)A machinery in primary prostate cancer. Furthermore, RNA interference assays of two prognostic m(6)A readers EIF3D and HNRNPA2B1 were conducted to explore m(6)A dependence of their functions in prostate cancer cell proliferation and migration. Results. A total of 41 mRNA m(6)A regulators have been identified to date. A small degree of copy number aberrations and an extremely low frequency of somatic mutations were observed in the regulators across prostate tumors. Enrichment of CpG sites and extensive changes of DNA methylation in the m(6)A machinery were also found. Impact of copy number variation on m(6)A regulator expression was stronger than that of DNA methylation disturbance. Furthermore, our study identified a set of m(6)A regulators related to clinical features and/or survival which were largely m(6)A-binding proteins. The translation initiation factor subunit EIF3D and the splicing factor HNRNPA2B1 can be independent prognostic factors which may contribute to retardation and promotion of cancer progression, respectively, through affecting cancer-related processes such as cell cycle. Moreover, in vitro assays demonstrated that m(6)A impacted the EIF3D and HNRNPA2B1 roles in proliferation and migration of prostate cancer cells. Conclusions. Our report systematically described molecular features of the mRNA m(6)A machinery and their potential roles in primary prostate cancer. Knowledge gained from this work may pave the way for further studies on the m(6)A system in prostate cancer.