Epi‐miRNAs: Modern mediators of methylation status in human cancers

Abstract

Methylation of the fundamental macromolecules, DNA/RNA, and proteins, is remarkably abundant, evolutionarily conserved, and functionally significant in cellular homeostasis and normal tissue/organism development. Disrupted methylation imprinting is strongly linked to loss of the physiological equilibrium and numerous human pathologies, and most importantly to carcinogenesis, tumor heterogeneity, and cancer progression. Mounting recent evidence has documented the active implication of miRNAs in the orchestration of the multicomponent cellular methylation machineries and the deregulation of methylation profile in the epigenetic, epitranscriptomic, and epiproteomic levels during cancer onset and progression. The elucidation of such regulatory networks between the miRNome and the cellular methylation machineries has led to the emergence of a novel subclass of miRNAs, namely "epi-miRNAs" or "epi-miRs." Herein, we have summarized the existing knowledge on the functional role of epi-miRs in the methylation dynamic landscape of human cancers and their clinical utility in modern cancer diagnostics and tailored therapeutics.

MIR145 Core Promoter Methylation in Pretreatment Cell-Free DNA: A Liquid Biopsy Tool for Muscle-Invasive Bladder Cancer Treatment Outcome

“…33 Focusing on BlCa, accumulating studies have reported cfDNA methylation as a potent biomarker for early diagnosis, prognosis, and monitoring of therapy responses. [34][35][36][37][38][39] In light of these findings, and along with the aberrant regulated levels of miR-143/145 in various malignancies and our previous published results on miR-143/145 cluster epigenetic regulation in bladder tumors, 19,40,41 we have studied the prognostic utility of MIR145 core promoter imprinting in pretreatment cfDNA.…”

Drug resistance in ovarian cancer: from mechanism to clinical trial

“…Most commonly, lncRNAs and circRNAs play roles in drug resistance by acting as miRNA sponges to regulate downstream gene expression [ 174 ]. “Epi-miRNAs” exert their effects by directly targeting epigenetic regulators, such as DNMTs and HDACs, or components of polycomb repressor complexes [ 175 ]. miRNAs affect mRNA transcription by binding to mRNA 3'-UTRs, leading to restoration of the expression of hypermethylated tumor suppressor genes [ 176 ].…”

Perspectives of microRNAs in bladder cancer and their potential as biomarkers for the early diagnosis of the disease

“…Evidence indicates that multiple miRNAs are dysregulated in most types of cancer 25 . Recent reports suggest that altered levels of miRNAs are directly related to tumor progression [26][27][28] , evasion of the immune response 29,30 , epigenetic reprogramming 31,32 , and metastasis [33][34] . It has been demonstrated that tumor cells secrete a large number of exosomes loaded with various molecules, including miRNAs 36,37 .…”