Reversal of Chemotherapy Resistance to Cisplatin in NSCLC by miRNA-195-5p via Targeting the FGF2 Gene

Hao Wang; Zhi-Lin Sui; Xian-Xian Wu; Peng Tang; Hong-Dian Zhang; Zhen-Tao Yu

doi:10.2147/PGPM.S302755

Reversal of Chemotherapy Resistance to Cisplatin in NSCLC by miRNA-195-5p via Targeting the FGF2 Gene

Pharmgenomics Pers Med. 2021 Apr 28:14:497-508. doi: 10.2147/PGPM.S302755. eCollection 2021.

Authors

Hao Wang^{1

2}, Zhi-Lin Sui¹, Xian-Xian Wu¹, Peng Tang¹, Hong-Dian Zhang¹, Zhen-Tao Yu^{1

3}

Affiliations

¹ Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy of Tianjin City, Tianjin, 300060, People's Republic of China.
² Department of Surgical Oncology, Baotou Cancer Hospital, Baotou, People's Republic of China.
³ Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, People's Republic of China.

Abstract

Objective: To explore the mechanism of miR-195-5p in the pathogenesis non-small cell lung cancer (NSCLC) and cisplatin resistance.

Methods: The function of miR-195-5p in NSCLC and cisplatin resistance were determined by MTT, scratch assay, transwell assay, and nude mice xenograft experiments. miR-195-5p target gene was identified by dual-luciferase reporter assays and real-time PCR analysis.

Results: miR-195-5p content was lower in A549/DDP than that in A549 cells, with reduced chemotherapy sensitivity and increased cell invasion and migration ability. The loss-of-function and gain-of-function assays illustrated that miR-195-5p might have increased the chemosensitivity to cisplatin in the A549/DDP cells and decreased cell migration and invasion. FGF2 is a negatively correlated action target of miR-195-5p. miR-195-5p might affect EMT by inhibiting FGF2. Overexpression of FGF2 resulted in enhanced cisplatin resistance in the cells, while miR-195-5p might have reversed this resistance.

Conclusion: Overall, miR-195-5p might target FGF2 to reduce cisplatin resistance in A549/DDP cells and enhance chemosensitivity.

Keywords: FGF2; NSCLC; chemosensitivity; cisplatin; miR-195-5p.

Grants and funding

This study was supported by the National Natural Science Foundation of China (Grant Number: 81772619, 82002551), Clinical Trial Project of Tianjin Medical University (Grant Number: 2017kylc006), and Bethune Charitable Foundation (Grant Number: HZB-20190528-18).