New insights into the interaction between m6A modification and lncRNA in cancer drug resistance

Abstract

Drug resistance is perhaps the greatest obstacle in improving outcomes for cancer patients, leading to recurrence, progression and metastasis of various cancers. Exploring the underlying mechanism worth further study. N6‐methyladenosine (m6A) is the most common RNA modification found in eukaryotes, playing a vital role in RNA translation, transportation, stability, degradation, splicing and processing. Long noncoding RNA (lncRNA) refers to a group of transcripts that are longer than 200 nucleotides (nt) and typically lack the ability to code for proteins. LncRNA has been identified to play a significant role in regulating multiple aspects of tumour development and progression, including proliferation, metastasis, metabolism, and resistance to treatment. In recent years, a growing body of evidence has emerged, highlighting the crucial role of the interplay between m6A modification and lncRNA in determining the sensitivity of cancer cells to chemotherapeutic agents. In this review, we focus on the recent advancements in the interaction between m6A modification and lncRNA in the modulation of cancer drug resistance. Additionally, we aim to explore the underlying mechanisms involved in this process. The objective of this review is to provide valuable insights and suggest potential future directions for the reversal of chemoresistance in cancer.

Abstract

In the past, most studies concerning m6A modification focused on mRNAs. Transcriptome‐wide mapping technology reveals a significant presence of m6A‐modified lncRNA, which has been shown to play vital roles in biological processes. Interestingly, the expressions and functions of m6A modification are also regulated by lncRNA in turn. The roles of m6A in the regulation of lncRNA mainly concentrate in following aspects: (1) Change the structure of lncRNA and affect its interaction with proteins, known as ‘m6A switch’. (2) Mediate gene transcription repression. (3) Mediate a competing endogenous RNA (ceRNA) model. (4) Regulates lncRNA stability or degradation. However, lncRNA has an impact on m6A regulators as well. LncRNA can influence the stability and degradation of m6A‐related enzyme proteins or combine with them to form interaction complexes, thus facilitating a regulatory effect on the downstream target mRNA of m6A regulators. Drug resistance is perhaps the greatest obstacle in improving outcomes for cancer patients, leading to recurrence, progression and metastasis of various cancers. In this review, we summarize all the identified interactions between m6A modification and lncRNA that participate in chemoresistance, aiming to provide a novel insight into the cancer treatment.