MicroRNA-34c-5p Reduces Malignant Properties of Lung Cancer Cells through Regulation of TBL1XR1/Wnt/β-catenin Signaling

• Published in: Current molecular medicine Vol. 24; no. 1; p. 114
• Main Authors: Lai, Weiqiang, Yue, Yonghong, Zeng, Ganhua
• Format: Journal Article
• Language: English
• Published: Netherlands 2024
• Subjects: beta Catenin - genetics; beta Catenin - metabolism; Catenins - genetics; Catenins - metabolism; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - genetics; Lung Neoplasms - pathology; MicroRNAs - genetics; MicroRNAs - metabolism; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Wnt Signaling Pathway - genetics; migration; microRNA-34c-5p; invasion; proliferation; TBL1XR1; Lung cancer
• ISSN: 1875-5666
• DOI: 10.2174/1566524023666230330083819

Lung cancer is common cancer with high mortality. A growing number of studies have focused on investigating the regulatory effects of microRNAs (miRs/miRNAs) during cancer progression. Nevertheless, the biological function of miR- 34c-5p in lung cancer and the underlying mechanism have not been determined. This study explored the effect of miR-34c-5p on the malignant behaviors of lung cancer cells. In this study, we utilized diverse public databases to obtain differentially expressed miRNAs. Then, qRT-PCR and western blot were conducted to determine miR-34c-5p and transducin β-like 1 X-linked receptor 1 (TBL1XR1) expression. Next, H1299 and H460 cells were transfected with miR-34c-5p-mimic and pcDNA3.1- TBL1XR1. To examine the anticancer effects of miR-34c-5p, CCK-8, scratch, and Matrigel-Transwell assays were conducted to test cell viability, migration, and invasion, respectively. The StarBase database and dual-luciferase reporter gene assay were used to predict and verify the relationship between miR-34c-5p and TBL1XR1. Finally, Wnt/β-catenin signaling- and epithelial-mesenchymal transition (EMT)- related protein levels were detected using western blot. The results demonstrated that miR-34c-5p was poorly expressed in lung cancer cells, while TBL1XR1 was highly expressed. The findings also confirmed the direct interaction between miR-34c-5p and TBL1XR1. In H1299 and H460 cells, miR-34c-5p overexpression inhibited cell proliferation, migration, and invasion, Wnt/β-catenin signaling activity, and EMT, while TBL1XR1 upregulation reversed these effects of miR-34c-5p overexpression. These findings illustrated that miR-34c-5p might repress the malignant behaviors of lung cancer cells via TBL1XR1, providing evidence for miR-34c-5p-based lung cancer therapy.