MiR-1244 sensitizes the resistance of non-small cell lung cancer A549 cell to cisplatin

Abstract

BackgroundCisplatin (DDP)-based chemotherapy is the mainstay of first-line therapy for lung cancer. However, their efficacy is often limited by the existence or development of chemoresistance. The aim of this study was to find and investigate the function of miRNAs in cisplatin (DDP)-resistant non-small cell lung cancer (NSCLC) A549 cell.MethodsQuantitative real-time PCR assay was employed to compare the differences of miRNA expression in both cisplatin-resistant A549 (A549/DDP) cell and the parental A549 cell. The dysregulated miRNAs were then corrected by transfecting oligonucleotides into A549/DDP cells. The cellular sensitivity to cisplatin, cell apoptosis and migration were conducted by MTT, flow cytometry and cell wound healing assay, respectively.ResultsBoth miR-589 and miR-1244 were significantly down-regulated in A549/DDP cell compared to the parental A549, while the expression of miR-182 and miR-224 were increased in A549/DDP cell (P < 0.05). Importantly, transfection of the cisplatin-resistant cells with either miR-589 or miR-1244 resulted in an increased sensitivity to cisplatin, indicating that the dysregulated miRNA may play an important role in chemotherapy resistance in cancer cell. The rescued expression of miRNA also reduced cell invasion and increased apoptosis of A549/DDP cell.ConclusionThe study indicates a crucial role of miR-1244 in the progress of cisplatin resistance of A549. Further understanding of miR-1244-mediated signaling pathways may promote the clinical use of miR-1244 in lung cancer therapy.

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

“…miR-487a has been associated to the transforming growth factor β1 (TGF-β1) pathway [48,49], a key cytokine in vascular function that has been previously related to estrogen action in endothelial cells [5]. On the other hand, our results showed miR-1244 as the most decreased miRNA in endothelial cells exposed to E2, which has been related to reduced migration of lung cancer cells [50]. As far as we know there is no published information about miRNA-1244, miR-501-3p, miR-4710 and miR-378h at cardiovascular level.…”

Shenqi Fuzheng Injection Reverses Cisplatin Resistance through Mitofusin‐2‐Mediated Cell Cycle Arrest and Apoptosis in A549/DDP Cells

“…Lung cancer is one of the most frequently diagnosed cancers across the globe, with non-small-cell lung cancer (NSCLC) accounting for nearly 85% of all lung cancer diagnoses [ 1 ]. Cisplatin-based chemotherapy is one of the most efficient therapeutic treatments for NSCLC; however, acquired drug resistance that develops during treatment is now a large barrier that negatively impacts the survival rate of patients [ 2 ].…”

Roles of microRNAs in the resistance to platinum based chemotherapy in the non-small cell lung cancer

“…Researchers have demonstrated the importance of microRNAs in CDDP resistance in NSCLC patients. In this review, we classified functions of microRNAs in CDDP resistance into three classes: Class A microRNAs regulate both CDDP resistance and EMT in NSCLC, like miR-129*(miR-129-1-3p), miR-200c, miR-17 family (-17, 20a, 20b), miR-15b, miR-27 and miR-181a 12 - 17 ; Class B includes microRNAs which regulate cell proliferation to contribute to CDDP resistance or sensitivity, such as the miR-17 family (-17, 20a, 20b), miR-217, miR-26a, miR-34a,miR-1, miR-26a, and miR-138 (19-23,25,26-27) ; Class C contains CDDP resistance related microRNAs which coordinate apoptosis of NSCLC cells, such as miR-31, Let-7c, miR-106a, miR-503, miR-497, miR-21, miR-184, miR-155, miR-137, mir-940, miR-92b and miR-138, miR-98-5p,miR-218, miR-1244, and miR-196 18 , 31 - 38 , 40 - 45 . Distinctions between the three classes are not absolute: for example, miR-34a reverses CDDP resistance and inhibits EMT, but also inhibits cell proliferation 22 - 25 .…”

“…MiR-218 can reverse CDDP resistance by decreasing runt-related transcription factor 2(RUNX2) 44 . MiR-1244 may enhance CDDP resistance probably by targeting TP53 45 . MiR-196a may confer CDDP resistance via inhibiting apoptosis probably by targeting human multiple drug resistance 1 (MDR1), multidrug resistance protein 1 (MRP1), excision repair cross-complementation 1 (ERCC1), survivin, and B cell lymphoma 2 (Bcl-2) 46 , 47 .…”