Long non-coding RNAs as molecular links and circulating biomarkers between type 2 diabetes and colorectal cancer: focus on shared signaling pathways, epigenetic regulation, and ubiquitination mechanisms

Type 2 Diabetes (T2D) and Colorectal Cancer (CRC) share a complex bidirectional relationship driven by common metabolic and inflammatory pathways. This review comprehensively examines the pivotal role of Long Non-Coding RNAs (lncRNAs) as molecular bridges between T2D and CRC, regulating gene expression at chromatin, transcriptional, and post-transcriptional levels. We focus on specific lncRNAs including H19, ANRIL, KCNQ1OT1, UCA1, GAS5, MIR31HG, HNF1A-AS1, and MALAT1, which modulate shared oncogenic and metabolic signaling cascades such as PI3K/AKT, Wnt/β-catenin, NF-κB, and HIF-1α. Furthermore, we expand the scope beyond isolated lncRNA regulation to emphasize the lncRNA-miRNA crosstalk and the systemic involvement of the cardiovascular system. Recent evidence highlights that miR-217, miR-122, and the NBAT1/miR-21 axis are critical regulators not only in CRC progression but also in myocardial injury associated with T2D. Consequently, we propose that a holistic biomarker strategy must integrate panels of both lncRNAs and miRNAs to capture the full spectrum of metabolic, oncogenic, and cardiac risks. This updated perspective underscores the translational potential of targeting multi-ncRNA networks for early diagnosis, prognosis, and therapeutic intervention in patients with multimorbidity.