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Published on: March 30, 2019
MicroRNA-503 Inhibits Non-Small Cell Lung Cancer Progression By Targeting PDK1/PI3K/AKT Pathway
Yingying Wei1, Yuanfan Liao2, Yu Deng2
1Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Objectives:
The aim of the study was to study the role of dysregulated expression of a microRNA (miRNA), miR-503, in non-small-cell lung cancer (NSCLC) and investigate the underlying mechanism.
Methods:
Quantitative real-time PCR (qRT-PCR) and in situ hybridization staining (ISH) were used to evaluate the expression level of miR-503 in NSCLC tissues and paired adjacent tissues. CCK-8, colony formation and flow cytometry were performed to explore the effects of miR-503 overexpression on cell proliferation, colony formation and apoptosis. Cells with miR-503 overexpression were used to initiate xenograft models. Dual luciferase reporter assay, qRT-PCR, immunohistochemistry and Western blotting were conducted to investigate the interaction of miR-503 and its potential target.
Results:
Significantly downregulated miR-503 was found in NSCLC tumor tissues and cell lines. miR-503 overexpression significantly inhibited NSCLC cell proliferation, migration and invasion. PDK1 was predicted as the direct targets of miR-503. PDK1 overexpression reversed the inhibitory effects of miR-503 on biological functions, while PDK1 silencing significantly counteracted miR-503 inhibitor-induced pro-tumor effects in A549 cells. Mechanistically, upregulation of miR-503 inhibited PDK1 expression and subsequently caused the inactivation of PI3K/AKT pathway.
Conclusion:
Our results suggest that miR-503 inhibits NSCLC progression by targeting PDK1/PI3K/AKT pathway, potentiating the use of miR-503 as a biomarker and therapeutic target for NSCLC.
Insights
MicroRNA miR-503 is downregulated in non-small-cell lung cancer (NSCLC). Restoring miR-503 inhibits NSCLC progression by targeting PDK1 and the PI3K/AKT pathway, suggesting its therapeutic potential.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Non-small-cell lung cancer (NSCLC) is a leading cause of cancer-related mortality.
- MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
- Dysregulation of specific miRNAs, like miR-503, is implicated in various cancers.
Purpose of the Study:
- To investigate the role of miR-503 in non-small-cell lung cancer (NSCLC).
- To elucidate the underlying molecular mechanism of miR-503's action in NSCLC.
- To evaluate miR-503 as a potential biomarker and therapeutic target for NSCLC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH) for miR-503 expression analysis.
- Cell proliferation, colony formation, and apoptosis assays to assess miR-503 function.
- Dual luciferase reporter assay, Western blotting, and immunohistochemistry to identify and validate miR-503 targets and pathways.
Main Results:
- miR-503 expression was significantly downregulated in NSCLC tissues and cell lines.
- Overexpression of miR-503 inhibited NSCLC cell proliferation, migration, and invasion.
- miR-503 directly targets PDK1, inhibiting the PDK1/PI3K/AKT signaling pathway and suppressing tumor progression.
Conclusions:
- miR-503 acts as a tumor suppressor in NSCLC by targeting PDK1 and inhibiting the PI3K/AKT pathway.
- Restoring miR-503 expression can impede NSCLC progression.
- miR-503 holds promise as a diagnostic biomarker and therapeutic agent for NSCLC.
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