Studying the inhibitory effects of miR-377 on EGFR gene in ErbB signaling pathway in A549 non-small cell lung cancer

Background: Aberrant expression and activity of ERBB pathway has been shown in some cancers including lung cancer and the results of many studies have shown that these receptors like EGFR and their aberrant activity have important role in cancer progression. MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as endogenous negative gene regulators. Recent studies suggest that abnormal expressions of miRNAs are involved in pathogenesis of different types of human cancers including lung cancer. In this study we aimed to investigate the effect of miR-377 on reverting the tumorigenic phenotype of lung cancer cell line by targeting EGFR.Methods: A549 was cultured. Pri-miRNA-377 and scrambled as negative control were transfected to cell line by lipofectamine (Invitrogen). mRNA was extracted by Tripure (Life Technology). Expression of mRNA was assessed by Quantitative PCR based. Proliferation and apoptosis of the cells were studied by MTT proliferation assay and staining the cells with Annexin-PI respectively. Results: We have shown that overexpression of miRNA-377 in lung cancer cell line (A549) decreased EGFR expression by Real Time PCR (P < 0.05) and miRNA-377 directly regulates expression of EGFR in A549 cell line. Furthermore, the enhanced expression of miRNA-377 could significantly inhibit cell proliferation and induce apoptosis (P < 0.05).Conclusion: The inhibition of ERBB pathway by targeting EGFR expression through miR-377 could be an important advance in targeted lung cancer therapy. Because of aberrant ERBB pathway activity in many cancers, the results of this study can be used as therapeutic line for other cancers.

کلیدواژه ها:

microRNA ، lung carcinoma ، EGFR