MiR-195-5p exerts tumor-suppressive functions in human lung cancer cells through targeting TrxR2. (17th December 2020)

• Record Type: Journal Article
• Authors: Bu, Lina; Tian, Yingxuan; Wen, Hongqing; Jia, Weihong; Yang, Shuanying
• Is Part Of: Acta biochimica et biophysica Sinica. Volume 53:Number 2(2021)
• Page Start: 189
• Page End: 200
• Publication Date: 2020-12-17
• Subjects: miR-195-5p -- TrxR2 -- lung adenocarcinoma -- tumor suppression; Biochemistry -- Periodicals; Biophysics -- Periodicals; 572.05
• DOI: 10.1093/abbs/gmaa159
• Languages: English
• ISSNs: 1672-9145

Abstract

Abstract: miR-195-5p has been widely explored in various cancers and is considered as a tumor-suppressive microRNA. However, its roles in human lung cancer pathogenesis are not fully elucidated. In this study, we aimed to explore how miR-195-5p is involved in malignant behaviors of lung adenocarcinoma (LUAD) cells. miR-195-5p expression was examined in the tumor tissues of patients with LUAD and human LUAD cell lines including A549 and PC-9. Thioredoxin reductase 2 (TrxR2) was predicted to be an mRNA target of miR-195-5p using online tools and validated by the Dual-Luciferase Reporter Assay. Lentivirus infection was used for gene overexpression, while gene knockdown was achieved by RNA interference. Cell proliferation was determined by Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine methods, and cell migration and invasion were assayed with transwell experiments. Cell apoptosis was determined by annexin V staining-based flow cytometry. The antitumor effects of miR-195-5p were also evaluated in nude mice xenografted with A549 cells. We found that miR-195-5p was lowly expressed in human LUAD cells, and its overexpression markedly suppressed cell proliferation, migration, and invasion and increased the apoptosis of LUAD cells in vitro . TrxR2 knockdown phenocopied the tumor-suppressive effects of miR-195-5p overexpression, while simultaneous TrxR2 overexpression remarkably reversed the effects of miR-195-5p overexpression on malignant behaviors of A549 and PC-9 cells. Additionally, miR-195-5p overexpression inhibited the growth of xenografted A549 tumor in nude mice. Our work verified that miR-195-5p exerts tumor-suppressive functions in LUAD cells through targeting TrxR2 and suggested that the miR-195-5p/TrxR2 axis is a potential biomarker for LUAD therapy.