Tehran University of Medical Sciences Basic & Clinical Cancer Research 2228-6527 16 1 2025 02 24 59 71 Mohammad Kordkatouli Department of Biology, Gorgan Branch, Islamic Azad University, Gorgan, Iran Mehr Ali Mahmood Janlou Department of Biology , Gorgan Branch, Islamic Azad University, Gorgan, Iran Audrius Dulskas Department of Abdominal and General Surgery and Oncology, National Cancer Institute, Vilnius, Lithuania Aryan Sateei Department of Biology , Gorgan Branch, Islamic Azad University, Gorgan, Iran 2024 10 26 2024 11 24 miR-31 is critically involved in the initiation and progression of CRC by regulating multiple pathways essential for tumorigenesis and influencing various cellular functions, such as proliferation, apoptosis, epithelial-mesenchymal transition (EMT), metastasis, and chemoresistance. miR-31 also impacts EMT-related transcription factors such as ZEB1, SNAIL, and TWIST, which further facilitate the shift to a mesenchymal state, leading to increased invasiveness and metastatic spread of CRC cells, commonly to organs like the liver, which worsens patient prognosis in the context of apoptosis, miR-31 inhibits pro-apoptotic factors such as BAX and Caspase-3, reducing programmed cell death and allowing cancer cells to survive longer this anti-apoptotic influence is essential for miR-31’s role in chemoresistance, as it enables cancer cells to evade the cytotoxic effects of chemotherapy. Interestingly, despite its primarily oncogenic role, miR-31 has shown context-dependent tumor-suppressive properties in specific genetic or environmental conditions under certain conditions, miR-31 may target oncogenes or reduce the activity of tumor-promoting pathways, although these instances are relatively rare and context-specific, influenced by factors like genetic mutations clinically, miR-31’s expression level is correlated with CRC stage, metastatic capacity, and patient prognosis, indicating its potential utility as a biomarker for risk assessment and prognosis. Elevated miR-31 levels are associated with advanced CRC stages, increased tumor aggressiveness, and poor overall survival, underscoring its relevance in patient management ongoing research is investigating miR-31 inhibitors as a therapeutic option to counteract its oncogenic effects and improve treatment responses by sensitizing CRC cells to chemotherapeutic-induced apoptosis. https://bccr.tums.ac.ir/index.php/bccrj/article/view/561