Elucidating The Roles of Signature Micrornas to Combat Cancer Drug Resistance in Oral Squamous Cell Carcinoma

Abstract

Resistance to chemotherapeutic drugs is a major obstacle to effective Oral Squamous cell carcinoma (OSCC) treatment, linked with tumor relapse. Compelling evidence has demonstrated that microRNAs (miRNAs) influence the development of cancer chemo resistance and tumorigenesis. Although multiple studies have shown the involvement of miRNAs in cancer chemo resistance, the exact molecular mechanisms in many cases are not clearly understood. In the current study, we intend to track down miRNA signature(s) and its associated targets imparting chemo resistance in OSCC. We analyzed array profiles of drug-resistant OSCC cells. We obtained 101 significantly dysregulated mRNAs targeted by 83 differentially expressed miRNAs, among which only 36 target genes are functionally enriched in tumorigenic and drug resistance-related pathways. Among the enriched miRNA­target duplexes, we found miR-185-Sp as a signature miRNA with FGFRLl as a top candidate target gene modulating chemo resistance in OSCC. Our qRT-PCR analysis validated that miR-185-Sp is significantly downregulated, while FGFRLl is significantly upregulated in the cisplatin-resistant SCC9 (CIS-R-SCC9) cell line, consistent with our findings from the array analysis. Subsequently, the gain of function study of miR-185-Sp by mimic transfection increases cisplatin sensitivity and decreases the migratory ability of CIS-R-SCC9 cell lines. Additional experiments are in progress to establish the involvement of this miRNA-target duo in imparting chemo resistance in oral cancer. This study will pave the way for finding therapeutic strategies employing miRNAs to combat chemo resistance in oral cancer.