The Complex Roles and Therapeutic Implications of m6A Modifications in Breast Cancer

Abstract

Accumulating evidence indicates that N6-methyladenosine (m6A), which directly regulates mRNA, is closely related to multiple biological processes and the progression of different malignancies, including breast cancer (BC). Studies of the aberrant expression of m6A mediators in BC revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such as Bcl-2 and the PI3K/Akt pathway, among others. Several regulators that target m6A have been shown to have anticancer effects. Fat mass and obesity-associated protein (FTO) was identified as the first m6A demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis. However, the exact mechanism by which m6A modifications are regulated by FTO inhibitors remains unknown. m6A modifications in BC have only been preliminarily studied, and their mechanisms require further investigation.

Dissecting the Role of N6-Methylandenosine-Related Long Non-coding RNAs Signature in Prognosis and Immune Microenvironment of Breast Cancer

“…Increasing evidence implicates that m6A regulators ("writers, " "erasers, " and "readers") exert an essential role in multiple types of cancer by regulation of the "epi-transcriptome" in cancers (Huang et al, 2020;Liu et al, 2020). Remarkably, both m6A "writers" and "erasers" regulators are abnormally overexpressed and perform an oncogenic role in BC (Wei et al, 2020). The long non-coding RNAs (lncRNAs), a large class of conserved endogenous RNAs, are characterized as transcripts longer than 200 nucleotides and no protein-coding potential (Statello et al, 2021).…”

“…N6-methyladenosine modification on RNA was involved in various stages of the RNA life cycle, including RNA transcription, processing, splicing, degradation, and RNA translation (Wei et al, 2020). m6A regulators act as either oncogenes or tumor suppressors to mediate the development and progression of BC.…”

The Prognostic Role of m6A-Related Genes in Paediatric Neuroblastoma Patients

“…m6A regulatory enzymes consist of “writers” (methyltransferases) METTL3, METTL14, RBM15, WTAP, VIRMA, and ZC3H13, “erasers” (demethylases) FTO and ALKBH5, and “readers” YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, IGF2BP1, IGF2BP2, IGF2BP3, HNRNPC, HNRNPG/RBMX, FMR1, and EIF3 [ 16 ]. Writers are responsible for catalyzing the formation of m6A modifications, erasers are responsible for removing m6A modifications, and readers are involved in the occurrence and development of human diseases by specifically identifying target RNAs modified by m6A.…”

Comprehensive Analysis of the Prognostic Role and Mutational Characteristics of m6A-Related Genes in Lung Squamous Cell Carcinoma

“…According to the characteristics of m6A proteins, they are divided as "writer, " "eraser, " and "reader" proteins, which dynamically regulate tumor-related pathological and physiological functions (Gu et al, 2020b). Many previous researches have proved the effects of N6-methyladenosine (m6A) RNA modification and its ability to regulate and coordinate related gene expression, whose level will profoundly affect cancer characteristics (Gu et al, 2020b;Shen et al, 2020;Wei et al, 2020). For example, in lung cancer, METTL3 acts as an oncogene, which increases the growth, survival, and invasion of lung adenocarcinoma cells (Lin et al, 2016).…”

“…Recently, studies on the prognostic role of m6A genes have emerged, including LUAD , renal cell carcinoma (Gao et al, 2020), cervical cancer (Yang et al, 2020), colorectal cancer (Sun et al, 2020), and breast cancer (Wei et al, 2020). However, few research focus on LUSC.…”