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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
LINC01082 Inhibits Non-Small Cell Lung Cancer by Targeting the miR-543/TNRC6A Axis
Ran Yang1,2, Jinli Han3, Song Zhao4
1Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, China.
Abstract:
Non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases and have poor clinical outcomes. Increasing number of lncRNAs are reported to be implicated in the carcinogenesis of NSCLC. Previous lncRNA-seq results showed that LINC01082 was under-expressed in several cancer types. In the current study, we focused on the role of LINC01082 in NSCLC development. An online bioinformatics tool was utilized to assess the expression profile of LINC01082, miR-543, and TNRC6A in NSCLC samples. RT-qPCR analysis was performed for evaluating LINC01082, TNRC6A and miR-543 expression in cells (NSCLC cells vs. normal lung cells). Impact of LINC01082 upregulation on cell proliferation in vitro was investigated by MTT and EdU experiments. Transwell assay was applied to analyze the migration and invasion of NSCLC cells. The cell apoptosis after plasmid transfection was detected by flow cytometry. The interactions among LINC01082, miR-543 and TNRC6A were measured by RNA pulldown and luciferase reporter assays. We showed that LINC01082 levels were downregulated in NSCLC samples and NSCLC cells. Overexpression of LINC01082 inhibited NSCLC cell proliferation, migration and invasion and strengthened cell apoptosis. LINC01082 directly bound to miR-543, and miR-543 targeted TNRC6A. TNRC6A was downregulated and miR-543 was overexpressed in NSCLC cells. miR-543 inhibition suppressed malignant cellular behaviors. TNRC6A knockdown reversed the effects of LINC01082 on the malignant character of NSCLC cells. In conclusion, LINC01082 exerts an antioncogenic role in NSCLC via interaction with miR-543 to regulate TNRC6A expression.
Insights
Long non-coding RNA LINC01082 suppresses non-small cell lung cancer (NSCLC) by inhibiting proliferation, migration, and invasion. It acts as an antioncogene by interacting with miR-543 to regulate TNRC6A expression in NSCLC.
Area of Science:
- Molecular Oncology
- Cancer Biology
- Non-coding RNA Research
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths with poor outcomes.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- LINC01082 has been found to be downregulated in various cancer types.
Purpose of the Study:
- To investigate the role of LINC01082 in the development of NSCLC.
- To elucidate the molecular mechanism of LINC01082 in NSCLC, including its interactions with miR-543 and TNRC6A.
Main Methods:
- Bioinformatic analysis of LINC01082, miR-543, and TNRC6A expression in NSCLC.
- RT-qPCR to quantify gene and miRNA expression.
- In vitro assays (MTT, EdU, Transwell, flow cytometry) to assess cell proliferation, migration, invasion, and apoptosis.
- RNA pulldown and luciferase reporter assays to confirm molecular interactions.
Main Results:
- LINC01082 expression was significantly downregulated in NSCLC tissues and cells.
- Overexpression of LINC01082 inhibited NSCLC cell proliferation, migration, and invasion, while promoting apoptosis.
- LINC01082 directly targets miR-543, which in turn targets TNRC6A. TNRC6A was downregulated and miR-543 overexpressed in NSCLC.
- Inhibition of miR-543 suppressed malignant behaviors, and TNRC6A knockdown reversed the antioncogenic effects of LINC01082.
Conclusions:
- LINC01082 functions as a tumor suppressor in NSCLC.
- The LINC01082/miR-543/TNRC6A axis plays a critical role in regulating NSCLC progression.
- LINC01082 may serve as a potential therapeutic target for NSCLC.
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