Cancer Management and Research (May 2021)
MiR-139-5p Targetedly Regulates YAF2 and Mediates the AKT/P38 MAPK Signaling Pathway to Alleviate the Metastasis of Non-Small Cell Lung Cancer Cells and Their Resistance Against Cisplatin
Abstract
Yubo Yan, Xiangyuan Jin, HaoBo Sun, Sainan Pang, Xianglong Kong, Jianlong Bu, Shidong Xu Department of Thoracic Surgery, Harbin Medical University Tumer Hospital, Harbin, Heilongjiang Province, 150000, People’s Republic of ChinaCorrespondence: Shidong XuDepartment of Thoracic Surgery, Harbin Medical University Tumer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150000, People’s Republic of ChinaTel +86-13903611962Email [email protected]: To explore relevant mechanisms of miR-139-5p in alleviating the metastasis of non-small cell lung cancer cells (NSCLC) and their resistance against cisplatin.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) assays were carried out to determine the protein levels of miR-139-5p and YAF2, and cisplatin (DDP)-resistant NSCLC cell strains were established. Subsequently, an MTT assay was employed to evaluate the viability of the cell strains, a Transwell assay to evaluate cell invasion activity, and flow cytometry to analyze cell apoptosis rate. Finally, a Western blot assay was carried out to determine the protein levels of P-PI3K and p-p38.Results: NSCLC tissues showed lower miR-139-5p expression and higher YAF2 expression than paracancerous tissues and human normal lung epithelial cells, and miR-139-5p was related to the prognosis of NSCLC patients. Overexpression of miR-139-5p or knock-down of YAF2 inhibited the proliferation and invasion of NSCLC cells and induced their apoptosis. Additionally, the dual-luciferase reporter assay verified a targeting relationship between miR-139-5p and YAF2. Overexpression of miR-139-5p and knockdown of YAF2 reversed the resistance of A549/DDP cells against DDP, inactivated p38 and Akt proteins, and inhibited the AKT/p38 MAPK signaling pathway. Furthermore, inhibiting the AKT/p38 MAPK signaling pathway with MK2206 resisted the effects of knock-down of miR-139-5p on DDP resistance in NSCLC cells.Conclusion: MiR-139-5p targetedly regulates YAF2 and mediates the AKT/p38 MAPK signaling pathway to alleviate the metastasis of NSCLC cells and their resistance against cisplatin, which may be a novel target for improving the therapeutic effect on NSCLC.Keywords: miR-139-5p, YAF2, AKT/p38 MAPK, non-small cell lung cancer, cisplatin
