An update on the molecular mechanisms underlying the progression of miR-21 in oral cancer.

Abstract

Globally, oral cancer ranks among the top ten cancers, with a higher prevalence in lower-income countries, where risk factors such as tobacco use, excessive alcohol consumption, and poor oral hygiene are widespread. Metastasis plays a critical role in cancer progression. miR-21 is a crucial regulator of cancer metastasis, profoundly influencing cellular and molecular pathways that contribute to tumour aggressiveness. As a microRNA, miR-21 downregulates tumour suppressor genes, promoting cell proliferation, survival, invasion, and migration. Its role in epithelial-mesenchymal transition (EMT) further facilitates metastatic behaviour. miR-21 also modulates the tumour microenvironment by promoting angiogenesis and altering immune responses, thus enhancing cancer progression.Moreover, miRNA - 21 influences the various signalling pathways like PI3K/ AKT, TGF-β, NF-κB, and STAT3, as well as involved in the cell fate mechanisms known as Autophagy and apoptosis. Clinically, elevated miR-21 levels are associated with poor prognosis, advanced tumour stages, and decreased survival rates, making it a valuable prognostic marker. Additionally, miR-21 expression levels can predict resistance to chemotherapy and targeted therapies, aiding in personalized treatment planning. Therapeutically, targeting miR-21 through anti-miR-21 oligonucleotides, small molecule inhibitors, and miRNA sponges shows promise in pre-clinical studies, potentially inhibiting tumour growth and improving sensitivity to existing treatments. Overall, miR-21's multifaceted role in cancer biology, its prognostic and predictive value, and its potential as a therapeutic target highlight its significance in advancing cancer diagnosis, treatment, and patient outcomes. Further research and clinical trials are essential to exploit miR-21's capabilities in oncology fully.