REVIEW article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Molecular Roles of microRNA-21 and Exosomal miR-21 in Gastrointestinal Cancers: Diagnostic, Therapeutic, and Drug Resistance Insights
Provisionally accepted
- 1Hebei North University Basic Medical College, Zhangjiakou, China
- 2The First Affiliated Hospital of Hebei North University, Zhangjiakou, China
- 3The Second Hospital of Hebei Medical University, Shijiazhuang, China
- 4Zhangjiakou First Hospital, Zhangjiakou, China
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MicroRNA-21 (miR-21) and its exosomal variant have gained recognition as pivotal molecular contributors to the etiology and advancement of gastrointestinal (GI) neoplasms, encompassing colorectal, gastric, pancreatic, and esophageal cancers. From a biosciences standpoint, miR-21 operates as a formidable oncomiR by inhibiting tumor suppressor genes, consequently fostering the dysregulated activation of crucial signaling cascades. The exosomal form of miR-21, released through tumor-derived extracellular vesicles, enhances intercellular interactions within the tumor microenvironment, influencing processes such as angiogenesis, immune evasion, epithelial-mesenchymal transition (EMT), and metastasis. Clinically, both tissue and circulating (serum/plasma) concentrations of miR-21 exhibit substantial potential as non-invasive biomarkers for the early detection, disease stratification, and prognostic assessment in gastrointestinal malignancies. Increased levels of exosomal miR-21 are associated with diminished overall survival, lymph node dissemination, and resistance to chemotherapeutic agents such as 5-fluorouracil, cisplatin, and gemcitabine. Mechanistically, exosomal miR-21 facilitates drug resistance by inhibiting apoptotic pathways and promoting cellular longevity through the modulation of the tumor microenvironment and stromal-tumor interactions. Therapeutically, bioscience-oriented strategies aimed at targeting miR-21 are currently under scrutiny to counteract chemoresistance and restore therapeutic effectiveness. These methodologies possess significant potential for applications in personalized medicine concerning gastrointestinal cancers. This review synthesizes contemporary biosciences perspectives on the molecular roles of miR-21 and exosomal miR-21, underscoring their diagnostic, prognostic, and therapeutic significance in gastrointestinal neoplasms. Particular emphasis is directed toward their involvement in overcoming drug resistance, thereby establishing them as promising targets for forthcoming translational oncology investigations.
Keywords: Gastrointestinal cancers, MicroRNA-21, Exosomes, diagnostics, Overcoming drug resistance
Received: 02 Sep 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Bai, Wang, Liu, Li, Wang and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Meiling Bai, baimeiling12@gmail.com
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