Novel insights into the interaction between N6‐methyladenosine methylation and noncoding RNAs in musculoskeletal disorders

Abstract

Background: Musculoskeletal disorder (MSD) are a class of inflammatory and degener-ative diseases, but the precise molecular mechanisms are still poorly understood. Noncoding RNA (ncRNA) N6-methyladenosine (m6A) modification plays an essential role in the pathophysiological process of MSD. This review summarized the interaction between m6A RNA methylation and ncRNAs in the molecular regulatory mechanism of MSD. It provides a new perspective for the pathophysiological mechanism and ncRNA m6A targeted therapy of MSD.Methods: A comprehensive search of databases was conducted with musculoskeletal disorders, noncoding RNA, N6-methyladenosine, intervertebral disc degeneration, osteoporosis, osteosarcoma, osteoarthritis, skeletal muscle, bone, and cartilage as the key-words. Then, summarized all the relevant articles.Results: Intervertebral disc degeneration (IDD), osteoporosis (OP), osteosarcoma (OS), and osteoarthritis (OA) are common MSDs that affect muscle, bone, cartilage, and joint, leading to limited movement, pain, and disability. However, the precise pathogenesis remains unclear, and no effective treatment and drug is available at present. Numerous studies confirmed that the mutual regulation between m6A and ncRNAs (i.e., microRNAs, long ncRNAs, and circular RNAs) was found in MSD, m6A modification can regulate ncRNAs, and ncRNAs can also target m6A regulators. ncRNA m6A modification plays an essential role in the pathophysiological process of MSDs by regulating the homeostasis of skeletal muscle, bone, and cartilage.Conclusion: m6A interacts with ncRNAs to regulate multiple biological processes and plays important roles in IDD, OP, OS, and OA. These studies provide new insights into the pathophysiological mechanism of MSD and targeting m6A-modified ncRNAs may be a promising therapy approach.

GRIK1‐AS1 deficiency accelerates endometriosis progression by boosting DNMT1‐dependent SFRP1 promoter methylation in endometrial stromal cells

“…[44][45][46] Significantly, a major regulatory function of nuclear lncRNAs is the modulation of the activity of several critical genes by coordinating with DNA epigenetic regulators, thus epigenetically influencing gene expression. 47 The majority of GRIK1-AS1 was found in the nucleus, and GRIK1-AS1 may directly interact with the DNA epigenetic controller DNMT1. Notably, our ROC curve analysis revealed that the better predictive performance that GRIK1-AS1 can be of prognostic value.…”

“…The essential roles of nucleus‐located lncRNAs are chromatin reorganization and transcription regulation 44–46 . Significantly, a major regulatory function of nuclear lncRNAs is the modulation of the activity of several critical genes by coordinating with DNA epigenetic regulators, thus epigenetically influencing gene expression 47 . The majority of GRIK1‐AS1 was found in the nucleus, and GRIK1‐AS1 may directly interact with the DNA epigenetic controller DNMT1.…”

Comprehensive analysis of the m6A-related molecular patterns and diagnostic biomarkers in osteoporosis

“…The above finding proved that the potential regulatory mechanism of m6A regulators modulated the process of OP. MiRNAs and lncRNAs are two targets that have recently come into the spotlight due to their regulatory ability to affect gene expression at the transcriptional or post-transcriptional levels and provide epigenetic modification ( 54 , 60 , 61 ). Here, we found that an m6A regulator (METTL3) and three m6A targets (SMAD4, HIPK3, and EGFR) might have a function in OP in an lncRNA–miRNA-dependent manner.…”

CircDOCK1 Regulates miR-186/DNMT3A to Promote Osteosarcoma Progression

“…Although the five-year survival was elevated over the last 3 decades for the OS population, their prognosis is still poor, making it necessary to discover new diagnostic and therapeutic targets for the management of OS [ 19 , 20 , 21 ]. The advantages of circRNA, such as its structural stability and tissue specificity, have attracted the attention of researchers in recent years [ 22 , 23 ]. Recent evidence suggests the close association of circRNA dysregulation with carcinoma progression and metastasis, including OS, indicating its potential as an OS therapeutic target [ 24 , 25 , 26 , 27 ].…”