Long Non-coding RNA NEAT1 in Colorectal Cancer: Molecular Mechanisms, Diagnostic Potential, and Resistance to Therapy

Colorectal cancer (CRC) is the malignancy with the 3rd highest incidence and 2nd highest mortality rates worldwide, showing the urgency of the implementation of therapy with high treatment effectiveness. Increased evidence has proven that the long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1), as the competing endogenous RNA (ceRNA), contributes to CRC progression through the modulation of several miRNA/protein axis, such as miRNA-216/YY1, miRNA-448/ZEB1, miRNA-34a/SIRT1, miRNA-486-5p/NR4A1, miRNA-185-5p/IGF2, miRNA-196a-5p/GDNF, miRNA-205-5p/VEGFA, miRNA-193a-3p/IL17RD, miRNA-193-3p/KRAS, miRNA-138/SLC38A1 and miRNA-495-3p/CDK6, as well as dysregulating several proteins, such as KDM5A, DDX5 and BHLHE40. This leads to the progression of epithelial-mesenchymal transition (EMT), Wnt/β-catenin signalling pathway, angiogenesis, cell cycle dysregulation and metabolic reprogramming. This review will comprehensively discuss the molecular mechanisms of NEAT1-mediated CRC progression, its role in therapy resistance, its potential as a biomarker for diagnosis purposes and the emerging therapeutic strategies for CRC.