Non‐coding RNAs and colitis‐associated cancer: Mechanisms and clinical applications

Abstract

Background Colitis‐associated cancer (CAC) is one of the most severe complications of inflammatory bowel disease (IBD), which has caused a worse survival rate in IBD patients. Although the exact aetiology and pathogenesis of CAC are not completely elucidated, evidence indicates that non‐coding RNAs are closely involved and play a key role. Methods This review aims to summarise the major findings of non‐coding RNAs in the development of CAC and present the potential mechanistic links between non‐coding RNAs and CAC pathogenesis. The results show that non‐coding RNAs can hinder DNA mismatch repair proteins and obstruct chromosome passenger complexes to increase microsatellite instability and accumulate chromosomal instability, respectively. The data also suggest that DNA promoter methylation or RNA methylation modifications of non‐coding RNA are the main mechanisms to regulate oncogene or tumour suppressor expression during the CAC progression. Other factors, including gut microbiota perturbations, immune dysregulation and barrier dysfunction, are also regulated and influenced by non‐coding RNAs. Besides, non‐coding RNAs as molecular managers are associated with multiple critical signalling pathways governing the initiation, progression and metastasis of CAC, including the janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor‐kappa B (NF‐κB), extracellular signal‐regulated kinase (ERK), Toll‐like receptor 4 (TLR4), Wnt/β‐catenin and phosphatidylinositol 3‐Kinase/Protein Kinase B (PI3K/AKT) pathways. In addition, non‐coding RNAs can be detected in colon tissues or blood, and their aberrant expressions and diagnostic and prognostic roles are also discussed and confirmed in CAC patients. Conclusions It is believed that a deepening understanding of non‐coding RNAs in CAC pathogenesis may prevent the progression to carcinogenesis, and will offer new effective therapies for CAC patients.

Methylation-Regulated Long Non-Coding RNA Expression in Ulcerative Colitis

“…The dysregulation of MIR4435-2HG in UC might play a key role in the inflammatory process and has been shown to be associated with CRC [ 37 , 42 , 43 ]. MIR4435-2HG is correlated with the expression of B cell lymphoma 2 (Bcl-2)-interacting protein (BCL2L11), which is associated with an increase in apoptosis resistance, resulting in impaired epithelial cell turnover [ 44 ].…”

Comprehensive Analysis of PANoptosis-Related Gene Signature of Ulcerative Colitis

“…In recent years, ceRNA crosstalk, or the interaction between miRNA and lncRNA, has played a critical role in immune-related diseases such as UC and tumors [ 45 , 46 , 47 ]. Studies have demonstrated that the expression of miR-449a is significantly reduced in colorectal cancer (CAC) tissues associated with colitis compared to paired adjacent non-cancerous tissues (ANT)[ 48 ]. Additionally, during the tumorigenesis process from UC to CAC, the level of miR-449a also exhibits a significant decrease [ 49 ].…”