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Published on: August 23, 2019
MicroRNA-34c-5p Reduces Malignant Properties of Lung Cancer Cells through Regulation of TBL1XR1/Wnt/β-catenin
Weiqiang Lai1, Yonghong Yue2, Ganhua Zeng1
1Department of Thoracic Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, 341000, P.R. China.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
MicroRNA-34c-5p (miR-34c-5p) inhibits lung cancer progression by downregulating transducin β-like 1 X-linked receptor 1 (TBL1XR1). This study shows miR-34c-5p represses malignant behaviors and EMT via TBL1XR1, suggesting its therapeutic potential.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Lung cancer is a leading cause of cancer mortality.
- MicroRNAs (miRNAs) play crucial roles in cancer progression.
- The specific function and mechanism of miR-34c-5p in lung cancer remain largely undetermined.
Purpose of the Study:
- To investigate the role of miR-34c-5p in the malignant behaviors of lung cancer cells.
- To elucidate the underlying molecular mechanism involving transducin β-like 1 X-linked receptor 1 (TBL1XR1).
Main Methods:
- Differential expression analysis using public databases.
- qRT-PCR and Western blot to assess miR-34c-5p and TBL1XR1 expression.
- Cell transfection, viability (CCK-8), migration (scratch), and invasion (Matrigel-Transwell) assays.
- Dual-luciferase reporter gene assay to confirm the interaction between miR-34c-5p and TBL1XR1.
- Analysis of Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT) markers.
Main Results:
- miR-34c-5p was significantly downregulated, while TBL1XR1 was upregulated in lung cancer cells.
- miR-34c-5p directly targets and represses TBL1XR1 expression.
- Overexpression of miR-34c-5p inhibited lung cancer cell proliferation, migration, invasion, Wnt/β-catenin signaling, and EMT.
- TBL1XR1 upregulation counteracted the inhibitory effects of miR-34c-5p.
Conclusions:
- miR-34c-5p acts as a tumor suppressor in lung cancer by inhibiting malignant behaviors.
- The mechanism involves the downregulation of TBL1XR1, Wnt/β-catenin signaling, and EMT.
- miR-34c-5p represents a potential therapeutic target for lung cancer treatment.
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