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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MiR-155 inhibits proliferation and invasion by directly targeting PDCD4 in non-small cell lung cancer
Feng Liu1,2,3, Dalong Song4,5,6, Yanhu Wu1
1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Background:
MicroRNAs are often abnormally expressed in human non-small cell lung cancer (NSCLC) and are thought to play a critical role in the emergence or maintenance of NSCLC by binding to its target messenger RNA. We assessed the effects of miR-155 on cell proliferation and invasion to elucidate the role played by miR-155/PDCD4 in NSCLC.
Methods:
Quantitative reverse transcription-PCR, Western blotting, and cell counting kit-8, luciferase, and transwell invasion assays were conducted on a normal human bronchial epithelial cell line (BEAS-2B) and three NSCLC cell lines (SPC-A-1, A549, and H2170).
Results:
We confirmed that miR-155 was upregulated, while PDCD4 messenger RNA and protein levels were downregulated in NSCLC cell lines. miR-155 negatively regulated PDCD4 at both transcriptional and post-transcriptional levels. Moreover, PDCD4 was forecast as an assumed target of miR-155 using bioinformatic methods and we demonstrated that PDCD4 was a direct target of miR-155 using luciferase reporter assays. Furthermore, PDCD4 overexpression could restrain NSCLC proliferation and invasion induced by miR-155.
Conclusion:
Our results collectively demonstrate that miR-155 exerts an oncogenic role in NSCLC by directly targeting PDCD4.
Insights
MicroRNA-155 (miR-155) promotes non-small cell lung cancer (NSCLC) by downregulating PDCD4. Overexpressing PDCD4 inhibits NSCLC cell growth and invasion, confirming miR-155
Area of Science:
- Molecular Oncology
- Cancer Biology
Background:
- MicroRNAs are frequently dysregulated in non-small cell lung cancer (NSCLC).
- MicroRNAs regulate gene expression and are implicated in NSCLC development.
- The role of miR-155 in NSCLC progression warrants further investigation.
Purpose of the Study:
- To investigate the role of miR-155 in NSCLC.
- To elucidate the regulatory relationship between miR-155 and PDCD4 in NSCLC.
- To assess the impact of miR-155 on NSCLC cell proliferation and invasion.
Main Methods:
- Quantitative reverse transcription-PCR and Western blotting were used to assess miR-155 and PDCD4 expression.
- Cell proliferation was measured using cell counting kit-8 assays.
- Cell invasion was evaluated using transwell invasion assays.
- Luciferase reporter assays confirmed the direct targeting of PDCD4 by miR-155.
Main Results:
- miR-155 was significantly upregulated in NSCLC cell lines compared to normal cells.
- PDCD4 mRNA and protein levels were downregulated in NSCLC cell lines.
- miR-155 directly targets PDCD4 at transcriptional and post-transcriptional levels.
- Overexpression of PDCD4 suppressed NSCLC cell proliferation and invasion.
Conclusions:
- miR-155 plays an oncogenic role in NSCLC.
- miR-155 promotes NSCLC progression by directly targeting and downregulating PDCD4.
- Targeting the miR-155/PDCD4 axis may offer a therapeutic strategy for NSCLC.
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