RNA m6A Methylation Regulators Multi-Omics Analysis in Prostate Cancer

Abstract

RNA N6-methyladenosine (m6A) methylation is known to be the most popular RNA modification in animals. Many research reports have elaborated on the effects of m6A regulators in medical practice, such as diagnosis, prognosis, and treatment. M6A modification has evident impacts on many aspects of RNA metabolism, just like RNA splicing, processing, translation, and stability. M6A also has a magnificent role in numerous types of cancers. We analyzed the prostate cancer datasets, from The Cancer Genome Atlas (TCGA) database, for every recognized m6A regulator in their gene expression, DNA methylation status and copy number variations (CNVs). We also systematically analyzed the relationship between different m6A regulators and the prognosis of prostate cancer. The results illustrated considerable differences in the expression of various m6A regulators between the prostate and normal cancer samples. At the same time, there were evident differences in the expression of various m6A regulators in prostate cancers with different Gleason scores. Subsequently, we determined CBLL1, FTO, YTHDC1, HNRNPA2B1 as crucial m6A regulators of prostate cancer. Premised on the expression of CBLL1, we also identified potential therapeutic agents for prostate cancer, and knockdown of HNRNPA2B1 prominently inhibited prostate cells migration and invasion in vitro experiment.

ELAVL1 promotes prostate cancer progression by interacting with other m6A regulators

“…Similarly, we also found that multiple m6A regulators were dysregulated in PCa. However, m6A regulators related to the progression-free interval, including CBLL1, EIF3A, ELAVL1, FTO, G2BP2, HNRNPA2B1, METTL3, and ZC3H13, were partially different from those including RBM15B, METTL3, HNRNPA2B1, RBMX, YTHDF1 and HNRNPC in a previous bioinformatic study (55). This discrepancy was due to the different samples included in our study.…”

“…Corresponding bioinformatics analysis studies have also found DNA mutations and CNVs of m6A regulators ( 54 ). A previous bioinformatic study of m6A regulators in PCa showed that the expression of most m6A regulators was dysregulated and that some regulators were related to survival ( 55 ). Similarly, we also found that multiple m6A regulators were dysregulated in PCa.…”

Epigenetic and Epitranscriptomic Control in Prostate Cancer

“…Recent computational studies have found a complex scenario in the expression of several writers, readers and erasers in PCa [ 145 , 146 , 147 , 148 , 149 ], suggesting the use of combined risk scores of several markers for prognosis prediction [ 145 , 147 , 148 ]. However, other studies have established a clear oncogenic role for increased m 6 A deposition ( Figure 2 B).…”

“…For example, METTL3 is overexpressed in PCa patients, leading to increased m 6 A RNA methylation [ 146 , 150 , 151 , 152 , 153 ]. In addition, several studies confirmed that METTL3 knocked-down (METTL3-KD) represses the proliferation, tumorigenic invasion, and migration capacity of PCa cells in a catalytic-dependent manner in vitro [ 149 , 150 , 151 , 152 , 153 ], and reduces tumour growth in vivo [ 150 ]. The downregulation of METTL3-mediated m 6 A methylation leads to the alteration of several downstream pathways.…”

From Omics to Multi-Omics Approaches for In-Depth Analysis of the Molecular Mechanisms of Prostate Cancer

“…They can focus on mRNAs but may include non-coding RNAs, such as miRNAs, lncRNAs or circular RNAs (circRNAs) [ 146 , 147 , 148 , 149 ]. RNA modifications, such as N6-methyladenosine methylation, are also being examined at a large scale due to their impact on stability and splicing [ 150 ]. The potential of gene expression data to provide additive value to traditional clinical parameters for disease progression prediction was shown several years ago in early microarray-based studies [ 151 ] and propelled the hunt for gene transcription signatures of disease recurrence and therapy response.…”