MicroRNA-mediated sensitization of lung cancer cells to chemotherapeutics: the roles of miR-21 and miR-155

Abstract

Background MicroRNAs (miRNAs) are conserved short 22-nucleotide RNAs with important roles in regulating gene expression. Misregulation of genes that control cell-cycle and cell-fate determination often contributes to cancer. The aims of this work were to evaluate the expressions of two oncogenic miRNA (oncomiRs), miR-21 and miR-155, in lung cancer, and to see whether reintroduction or inhibition of these would affect progression or aid sensitivities of the lung cancer cells to major chemotherapeutics. Methods This work involved cell culture of lung adenocarcinoma cells H358 and A549 and normal lung cells. It compared the miRNA expression profiles of two miRNAs (miR-21 and miR-155) in cancer and normal lung cell lines using real-time PCR and then treated with three known chemotherapeutics, namely cisplatin, etoposide and paclitaxel, and concluded by inhibiting overexpressed miRNA by transfecting the cancer cells with miRNA inhibitors, and proliferation was measured with sulforhodamine-B assay. Results showed that miR-21 was overexpressed in the entire cell lines used, which is consistent with the role of miR-21 as an oncomir, whereas miR-155 was downregulated, suggesting that miR-155 could be acting as a tumor suppressor. Furthermore, inhibition of miR-21 function in H358 lines using 50 nM Ambion anti-miR led to a decreased proliferation of H358 cells compared with the 50 nM anti-miR-155-treated group. Downregulation of miR-21 seems to sensitize lung cancer cells to chemotherapeutics (etoposide). Conclusion This work demonstrated that miR-21 at 50 nM might sensitize lung cancer cells to chemotherapeutics (etoposide) and that miR-155, a known oncogenic miRNA, seems to be acting as a tumor suppressor in lung cancer, which promises to be of immense therapeutic importance.