Systematic Investigation of mRNA N6-Methyladenosine Machinery in Primary Prostate Cancer

Abstract

Background. Appreciable findings have pointed out pivotal roles of N6-methyladenosine (m6A) 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 m6A machinery. Multiomics integration was performed to systematically investigate the mRNA m6A machinery in primary prostate cancer. Furthermore, RNA interference assays of two prognostic m6A readers EIF3D and HNRNPA2B1 were conducted to explore m6A dependence of their functions in prostate cancer cell proliferation and migration. Results. A total of 41 mRNA m6A 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 m6A machinery were also found. Impact of copy number variation on m6A regulator expression was stronger than that of DNA methylation disturbance. Furthermore, our study identified a set of m6A regulators related to clinical features and/or survival which were largely m6A-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 m6A impacted the EIF3D and HNRNPA2B1 roles in proliferation and migration of prostate cancer cells. Conclusions. Our report systematically described molecular features of the mRNA m6A machinery and their potential roles in primary prostate cancer. Knowledge gained from this work may pave the way for further studies on the m6A system in prostate cancer.

RNA m6A Methylation Regulators Multi-Omics Analysis in Prostate Cancer

“…Some researchers found 41 mRNA m6A regulators have been identified to play critical roles in primary prostate cancer. The translation initiation factor subunit EIF3D may delay the prostate cancer progression while the splicing factor HNRNPA2B1 may promote prostate cancer progression, in vitro assays proved the roles of EIF3D as well as HNRNPA2B1 in prostate cancer cells (Jiang et al, 2020). It was found that the expression of METTL14, IGF2BP3, HNRNPA2B1, and CNV of ALKBH5 were linked to the recurrence-free survival of prostate cancer.…”

Construction of a risk prediction model using m6A RNA methylation regulators in prostate cancer: comprehensive bioinformatic analysis and histological validation

“…It has been reported that upregulation of HNRNPA2B1 by PCAT6 promotes PCa progression and neuroendocrine differentiation [ 41 ]. HNRNPA2B1 may also be an independent prognostic factor and contribute to cancer progression [ 42 ]. Coexpression network analysis using clinical data from the GSE70768 dataset as well as quantitative proteomic mass spectrometry profiling and gene enrichment analysis using LNCaP and PC3 cell lines suggest that HNRNPA2B1 is associated with PCa progression and prognosis [ 43 , 44 ].…”

Construction of risk prediction model using m6A RNA methylation regulators in prostate cancer: comprehensive bioinformatic analysis and histological validation

“…It has been reported that upregulation of HNRNPA2B1 by PCAT6 promotes PCa progression and neuroendocrine differentiation [39]. HNRNPA2B1 may also be an independent prognostic factor and contribute to cancer progression [40]. Coexpression network analysis using clinical data from the GSE70768 dataset as well as quantitative proteomic mass spectrometry pro ling and gene enrichment analysis using LNCaP and PC3 cell lines suggest that HNRNPA2B1 is associated with PCa progression and prognosis [41,42].…”