Upregulation Of MicroRNA-451 Increases Cisplatin Sensitivity Of Non-small Cell Lung Cancer Cell Line(A549)

BackgroundNon small cell lung cancer comprises 70 %～80 % of a11 cases of bronchogenic carcinoma, More than 60% of patients with advanced, often lose the chance of operation. chemotherapy is the mainstay treatment. DDP still remains the most widely used first-line chemotherapeutic agent for the IIIb-IV NSCLC treatment. but,the chemotherapy is not efficient. which is a major problem in lung cancer treatment. Therefore, improving the sensitivity to drug doses strategies is a key for the chemotherapy efficacy.MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that have been identified as post-transcriptional regulators of gene expression. MiRNAs exert their functions through imperfect base-pairing with the 3'- untranslated region (3'-UTR) of target mRNAs. In human cancer, miRNAs can act as oncogenes or tumour suppressor genes during tumourigenesis. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer. Recently, miR-451 as a tumor suppressor has been reported in other studies. recent researches have show that miR-451 could improve the sensitivity of DOX-resistant breast cancer cells (MCF-7/DOX) to doxorubicin. However, to our best knowledge, there have been no reports about the association of miR-451 expression with the sensitivity of chemotherapy in NSCLC.Objective:The aim of this study is to evaluate the efficacy and mechanism of miR-451 in the growth and sensitivity of chemotherapy in NSCLC.Methods:Quantitative RT-PCR assay was performed to detect the expression of miR-451 in 10 pairs of NSCLC and noncancerous tissue samples.QcDNA-GW/EmGFP-miR-451 was stably transfected into NSCLC cell line (A549). quantitative RT-PCR detect the expression of miR-451 in the stably transfected cell. Then, detect the effects of miR-451 upregulation on growth, colony formation and apoptosis of A549 cells by MTT, flow cytometry, Colony formation and Hoechst staining. The Western blot and TUNEL was used to assay apoptosis relative proteins Finally, the effects of miR-451 upregulation on in vitro and in vivo sensitivity of A549 cells of DDP were also determined.Results:The level of miR-451 expression in NSCLC tissues was significantly higher than that in corresponding noncancerous tissues. Ectopic overexpression of miR-451 could significantly inhibit growth and induce apoptosis of A549 cells. Moreover, ectopic overexpression of miR-451 could sensitize A549 cells to DDP possibly by increasing DDP-induced apoptosis which might be associated with the inactivation of Akt signaling pathway.Conclusions:In the present study, we found that the upregulation of miR-451 could significantly inhibit growth and enhance DDP chemosensitivity in NSCLC cell line (A549) by inducing apoptosis enhancement.