Cancer Management and Research (Aug 2020)
MiR-26a-5p Serves as an Oncogenic MicroRNA in Non-Small Cell Lung Cancer by Targeting FAF1
Abstract
Ming-fan Ye,1,* Dong Lin,2,* Wu-jin Li,1 Hai-peng Xu,2 Jing Zhang2 1Department of Chest Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Thoracic Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Zhang Tel +86 13809557405Email [email protected]: Non-small cell lung cancer (NSCLC) accounts for approximately 80– 85% of all lung cancers, with the FAS-associated factor 1 (FAF1) acting as a tumor suppressor. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we aimed to reveal the influence of miR-26a-5p on the regulation of FAF1 expression and NSCLC progression, with the motivation of identifying a potential therapeutic target for NSCLC treatment.Methods: A dual-luciferase reporter assay was used to check for the direct targeting of FAF1 by miR-26a-3p. The miR-26a-5p inhibitor or FAF1 shRNA plasmid was transfected into A549 and H1299 cells to modulate FAF1 expression. Then, the effect of miR-26a-5p/FAF1 on cellular functions was investigated. MTT assay was used to evaluate cell viability. EdU proliferation assay and cell cycle assay were performed to analyze the effect of miR-26a-5p on cell replication and cell cycle. We used annexin V-FITC and PI to stain apoptotic cells, followed by flow cytometric analysis. Transwell and wound healing assays were performed to investigate metastasis. Moreover, the effect of miR-26a-5p/FAF1 on cancer progression was examined in vivo. Lastly, the underlying mechanism was uncovered using RT-qPCR, Western blotting, and TOP/FOP flash assay.Results: miR-26a-5p was found to directly target FAF1 and downregulate its expression. Blocking miR-26a-5p inhibited the cell growth, migration, and invasion, but promoted cell apoptosis. In addition, this inhibited the growth of tumor in mice. FAF1 knockdown reversed the functions of miR-26a-5p. Further, miR-26a-5p/FAF1 was observed to play an important role in the Wnt signaling pathway, regulating the expression of genes such as AXIN, c-Myc, and cyclin-D1.Conclusion: Taken together, we show that miR-26a-5p functions as an oncogenic microRNA in NSCLC by targeting FAF1 and may serve as a potential target for NSCLC treatment.Keywords: miR-26a-5p, FAF1, NSCLC, proliferation, apoptosis, metastasis
