Biological role of prognostic microRNAs (miRNAs) in squamous lung carcinoma (SCC) cells

Abstract

Background and Aim: To date, there are no reliable tools allowing for individual selection of high-risk non-small cell lung cancer (NSCLC) patients for adjuvant chemotherapy. We earlier demonstrated that overexpression of three miRNAs: miR-662, -192 and -192* may correlate with the risk of distant relapse in SCC patients undergoing pulmonary resection (Skrzypski et al. 2014, Br J Cancer). The aim of this study was to assess the biological role of three abovementioned miRNAs in SCC cells. Methods: We screened by reverse transcription quantitative PCR (RT-qPCR) 11 NSCLC cell lines for miRNA expression profiles and assessed their sensitivity for cisplatin and etoposide by MTT cytotoxic test. Cells naturally overexpressing miR-662, -192 and -192* were transfected with locked nucleic acid (LNATM) miRNA inhibitors. The inhibitor-treated and WT cells were compared in cytotoxic and proliferation MTT tests and soft agar colony formation assay. Results: Among analyzed NSCLC cell lines we found a SCC cell line with natural overexpression of miR-662, -192 and -192*. These cells were resistant to chemotherapeutics and exhibited an ability to form colonies in soft agar. The inhibition of miR-192, -192* and -662 sensitized SCC cells for cisplatin and etoposide. Moreover, we observed reduced proliferation and soft agar colony number in comparison to negative control (p<0.001). Conclusions: Our results suggest that genes regulated by miR-192, miR-192* and/or miR-662 may be involved in maintaining the chemoresistance and clonogenic potential of SCC. Further studies may elucidate predictive value of these genes. Also, miRNAs may serve as promising targets for novel treatment strategies.