Systematic Investigation of mRNA -Methyladenosine Machinery in Primary Prostate Cancer.

Background: Appreciable findings have pointed out pivotal roles of -methyladenosine (mA) 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 mA machinery. Multiomics integration was performed to systematically investigate the mRNA mA machinery in primary prostate cancer. Furthermore, RNA interference assays of two prognostic mA readers EIF3D and HNRNPA2B1 were conducted to explore mA dependence of their functions in prostate cancer cell proliferation and migration.

Results: A total of 41 mRNA mA 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 mA machinery were also found. Impact of copy number variation on mA regulator expression was stronger than that of DNA methylation disturbance. Furthermore, our study identified a set of mA regulators related to clinical features and/or survival which were largely mA-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, assays demonstrated that mA impacted the EIF3D and HNRNPA2B1 roles in proliferation and migration of prostate cancer cells.

Conclusions: Our report systematically described molecular features of the mRNA mA machinery and their potential roles in primary prostate cancer. Knowledge gained from this work may pave the way for further studies on the mA system in prostate cancer.