Novel insights into the multifaceted roles of m6A-modified LncRNAs in cancers: biological functions and therapeutic applications

Abstract

N6-methyladenosine (m6A) is considered as the most common and important internal transcript modification in several diseases like type 2 diabetes, schizophrenia and especially cancer. As a main target of m6A methylation, long non-coding RNAs (lncRNAs) have been proved to regulate cellular processes at various levels, including epigenetic modification, transcriptional, post-transcriptional, translational and post-translational regulation. Recently, accumulating evidence suggests that m6A-modified lncRNAs greatly participate in the tumorigenesis of cancers. In this review, we systematically summarized the biogenesis of m6A-modified lncRNAs and the identified m6A-lncRNAs in a variety of cancers, as well as their potential diagnostic and therapeutic applications as biomarkers and therapeutic targets, hoping to shed light on the novel strategies for cancer treatment.

LINC01134: a pivotal oncogene with promising predictive maker and therapeutic target in hepatocellular carcinoma

“…The potential of lncRNAs as therapeutic targets in cancer treatment is increasingly recognized ( 24 , 28 ), and LINC01134, a newly identified lncRNA, emerges as a promising candidate for HCC therapy. Experimental evidence from multiple studies ( 42 – 45 , 49 – 52 ) has elucidated the regulatory role of LINC01134 in HCC development, highlighting its influence on key molecules and genes pivotal for tumorigenesis and disease progression ( Figure 6 ).…”

RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy

“…m6A mainly acts by directly altering the RNA modification of metabolic enzymes and transporters or indirectly affecting related metabolic molecules 10 . For example, long non‐coding RNAs (lncRNAs) are important regulators of processes such as epigenetic modification, transcription and post‐transcriptional translation and have been shown to be one of the main targets of m6A methylation 11 . RNA modification was originally designed to adjust the structure of ncRNAs.…”

“… 10 For example, long non‐coding RNAs (lncRNAs) are important regulators of processes such as epigenetic modification, transcription and post‐transcriptional translation and have been shown to be one of the main targets of m6A methylation. 11 RNA modification was originally designed to adjust the structure of ncRNAs. However, with the discovery of more and more post‐transcriptional regulators, they are now considered to be dynamically regulated.…”

FTO promotes the progression of bladder cancer via demethylating m6A modifications in PTPN6 mRNA

“…In the context of BC, understanding the significance of epigenetic abnormalities, including those occurring at multiple levels of DNA, RNA, and histone modification, is critical for elucidating the molecular mechanisms underlying BC progression and developing targeted therapeutic strategies. Epigenetic alterations, such as aberrant DNA methylation, histone modifications, and dysregulated non-coding RNA expression, have been implicated in various aspects of BC pathogenesis, including tumor initiation, progression, metastasis, and treatment resistance [ 13 , 14 ]. Specifically focusing on m6A RNA methylation, emerging evidence suggests its involvement in regulating gene expression and mRNA metabolism in cancer, including BC [ 15 , 16 ].…”