OncoTargets and Therapy (Jan 2020)
miR-1269b Drives Cisplatin Resistance of Human Non-Small Cell Lung Cancer via Modulating the PTEN/PI3K/AKT Signaling Pathway
Abstract
Wu Yang,1 Wei Xiao,2 Zhengrong Cai,3 Shidai Jin,1 Tian Li3 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, People’s Republic of China; 2Department of Radiotherapy, Nanjing Chest Hospital, Nanjing, Jiangsu Province 210029, People’s Republic of China; 3Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu Province 210029, People’s Republic of ChinaCorrespondence: Shidai JinDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, People’s Republic of ChinaEmail [email protected] LiDepartment of Respiratory Medicine, Nanjing Chest Hospital, No. 215 Guangzhou Road, Nanjing, Jiangsu Province 210029, People’s Republic of ChinaEmail [email protected]: MiRNAs have been reported to induce certain drug resistance in multiple solid tumors via various mechanisms. Our study aimed to investigate whether miRNA-1269b was involved in the chemoresistance and the progression of non-small cell lung cancer (NSCLC).Methods: MTT and colony formation assay were conducted to determine cell proliferation and cell apoptosis was analyzed by flow cytometry with annexin V/PI. Luciferase reporter assay was performed to validate miRNA-targeting sequences. The function of miR-1269b in cisplatin-resistant was evaluated in vivo in a mouse tumor model.Results: We found that miR-1269b expression was up-regulated in cisplatin-resistant NSCLC specimens and NSCLC cell lines, which resulted in the promotion of chemoresistance and tumorigenicity. miR-1269b overexpression enhanced drug resistance and promoted cell proliferation in vitro and tumor growth in vivo, with reduced apoptosis rate of A549 cells inin vitro cell culture. Mechanistically, we identified PTEN as the direct target of miR-1269b, and the PTEN level was negatively correlated with miR-1269b in NSCLC specimens. Further study demonstrated that miR-1269b targeted PTEN to modulate PI3K/AKT signaling pathway.Conclusion: In conclusion, these findings suggest that the miR-1269b/PTEN/PI3K/AKT-mediated network might promote cisplatin resistance in NSCLC, and that miR-1269b can be a potential therapeutic target for chemoresistance in NSCLC patients.Keywords: miR-1269b, NSCLC, cisplatin resistant, PTEN, PI3K/AKT signaling
