Long non-coding RNAs in the crosstalk between diabetes and colorectal cancer: molecular mechanisms and endocrine pathways

Abstract

Colorectal cancer (CRC) and diabetes mellitus are major global health burdens that frequently coexist and share overlapping metabolic and molecular abnormalities. Accumulating epidemiological evidence indicates that diabetes is associated with an increased risk of CRC; however, the underlying mechanisms remain incompletely defined. Long non-coding RNAs (lncRNAs) have recently emerged as important regulators of gene expression and cellular signaling, with critical roles in both metabolic disorders and cancer. In this review, we summarize current evidence on key lncRNAs that are implicated in the shared molecular networks linking diabetes and CRC. These lncRNAs modulate multiple signaling pathways, including PI3K/AKT, Wnt/β-catenin, NF-κB–mediated inflammation, hypoxia-associated signaling, metabolic reprogramming, angiogenesis, and epigenetic regulation. Through interactions with microRNAs (miRNAs), transcription factors, and chromatin-modifying complexes, they influence key biological processes such as insulin signaling, glucose metabolism, epithelial–mesenchymal transition, oxidative stress responses, and tumor progression. Elucidating the roles of lncRNAs provides important insight into the molecular interplay between metabolic dysfunction and colorectal tumorigenesis. Notably, many lncRNAs are detectable in circulating fluids, highlighting their potential as non-invasive biomarkers for early detection and risk assessment in diabetic populations at increased risk of CRC. Furthermore, targeting dysregulated lncRNAs may offer novel therapeutic opportunities to simultaneously modulate metabolic and oncogenic pathways. Overall, integrating lncRNA biology into the study of CRC and diabetes may advance our understanding of disease mechanisms and support the development of improved diagnostic and therapeutic strategies.