Drug resistance in oral cancer is one of the major problems in oral cancer therapy because therapeutic failure directly results in tumor recurrence and eventually in metastasis. Accumulating evidence has demonstrated the involvement of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in processes related to the development of drug resistance. A number of studies have shown that ncRNAs modulate gene expression at the transcriptional or translational level and regulate biological processes, such as epithelial-to-mesenchymal transition, apoptosis, DNA repair and drug efflux, which are tightly associated with drug resistance acquisition in many types of cancer. Interestingly, these ncRNAs are commonly detected in extracellular vesicles (EVs) and are known to be delivered into surrounding cells. This intercellular communication via EVs is currently considered to be important for acquired drug resistance. Here, we review the recent advances in the study of drug resistance in oral cancer by mainly focusing on the function of ncRNAs, since an increasing number of studies have suggested that ncRNAs could be therapeutic targets as well as biomarkers for cancer diagnosis.

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