The role of RNA modification in urological cancers: mechanisms and clinical potential

Abstract

RNA modification is a post-transcriptional level of regulation that is widely distributed in all types of RNAs, including mRNA, tRNA, rRNA, miRNA, and lncRNA, where N6-methyladenine (m6A) is the most abundant mRNA methylation modification. Significant evidence has depicted that m6A modifications are closely related to human diseases, especially cancer, and play pivotal roles in RNA transcription, splicing, stabilization, and translation processes. The most common urological cancers include prostate, bladder, kidney, and testicular cancers, accounting for a certain proportion of human cancers, with an ever-increasing incidence and mortality. The recurrence, systemic metastasis, poor prognosis, and drug resistance of urologic tumors have prompted the identification of new therapeutic targets and mechanisms. Research on m6A modifications may provide new solutions to the current puzzles. In this review, we provide a comprehensive overview of the key roles played by RNA modifications, especially m6A modifications, in urologic cancers, as well as recent research advances in diagnostics and molecularly targeted therapies.

RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations

“…Our investigation provides an in-depth exploration of the intricate landscape of RNA m6A methylation, a prominent epitranscriptomic modification within the context of PCa. Recent recognition of m6A's pivotal roles in mRNA regulation, stability, and translation has sparked interest in its potential involvement in tumorigenesis, tumor development, and clinical applications [6,7,15,19].…”

“…The chemical modification of biological macromolecules is a highly specific regulatory mechanism in many diseases, including cancer [6][7][8][9]. Currently, more than 170 RNA modifications have been identified, composing the human "epitranscriptome" [10].…”

“…Although the evidence highlights aberrant m6A regulation patterns in multiple cancers, the mechanism underlying the regulatory role of m6A modification in cancer progression remains incompletely understood. The overexpression of m6A regulators has been implicated in tumorigenesis in lung cancer, breast cancer, and certain gynecological tumors, yet conflicting roles of m6A regulators persist in other cancer types [6,7,15]. Therefore, precise profiling of m6A-regulator-based signatures is crucial for investigating the diverse regulatory impact of m6A regulators on cancer progression, survival, and drug resistance.…”

Role of N6‑methyladenosine in the pathogenesis, diagnosis and treatment of prostate cancer (Review)

“…The knockdown of METTL3 leads to an increase in the key regulatory factor lysine-specific demethylase-1. Lysine-specific demethylase-1 is involved in the development of PCa and affects the expression and function of AR ( 127 ). The high expression of HNRNPA2B1 can promote the proliferation and metastasis of PCa.…”

“…This suggests that m 6 A modification may also be involved in the regulation of tumor-related genes. In addition, the association between changes in the expression levels of three types of partial regulators in PCa, and the development and progression of PCa have been demonstrated ( 113 , 127 ). The three regulators interact to specifically regulate RNA splicing, translation, stability and other aspects in an m 6 A-dependent manner, and promote specific biological behaviors such as proliferation, migration, and invasion of cancerous tissues.…”