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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-29a plays a suppressive role in non-small cell lung cancer cells via targeting LASP1
Zhaolan Hu1, Yanhui Cui1, Yanhui Zhou2
1Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University.
Abstract:
MicroRNA (miR)-29a has been implicated in non-small cell lung cancer (NSCLC), but the mechanism remains largely unclear. LASP1, a cAMP- and cGMP-dependent signaling protein, was recently found to promote proliferation and aggressiveness in NSCLC. However, the regulatory mechanism of LASP1 expression in NSCLC, as well as the relationship between LASP1 and miR-29a, has never been previously studied. In this study, we found that miR-29a was remarkably downregulated and low expression of miR-29a was associated with the malignant progression of NSCLC. Moreover, the expression of LASP1 was markedly increased in NSCLC tissues and cell lines. Bioinformatics analysis and luciferase reporter assay data further identified LASP1 as a target gene of miR-29a, and the expression of LASP1 was negatively mediated by miR-29a at the post-transcriptional level in NSCLC cells. Overexpression of miR-29a reduced the proliferation, migration, and invasion of NSCLC cells, just as the effects of LASP1 knockdown. Moreover, overexpression of LASP1 attenuated the suppressive effect of miR-29a on the malignant phenotypes of NSCLC cells. In addition, upregulation of miR-29a decreased the growth of A549 cells in nude mice and protected the animals from tumor-induced death. Therefore, we demonstrate that miR-29a plays a suppressive role in NSCLC via targeting LASP1, suggesting that the miR-29a/LASP1 axis may become a promising therapeutic target for NSCLC.
Insights
MicroRNA (miR)-29a suppresses non-small cell lung cancer (NSCLC) by downregulating LASP1. This miR-29a/LASP1 axis offers a potential therapeutic target for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNA (miR)-29a is linked to non-small cell lung cancer (NSCLC), but its precise role is unclear.
- LASP1, a protein promoting NSCLC proliferation and aggressiveness, has an unstudied regulatory mechanism in this cancer.
- The relationship between LASP1 and miR-29a in NSCLC has not been previously investigated.
Purpose of the Study:
- To elucidate the mechanism of miR-29a in NSCLC progression.
- To identify the regulatory relationship between miR-29a and LASP1 in NSCLC.
- To explore the potential of the miR-29a/LASP1 axis as a therapeutic target for NSCLC.
Main Methods:
- Bioinformatics analysis to predict gene targets.
- Luciferase reporter assays to validate gene regulation.
- In vitro cell culture experiments (proliferation, migration, invasion assays) and in vivo xenograft models in nude mice.
Main Results:
- miR-29a was significantly downregulated in NSCLC, correlating with malignant progression.
- LASP1 expression was markedly increased in NSCLC tissues and cell lines.
- LASP1 was identified as a direct target of miR-29a, with miR-29a negatively regulating LASP1 post-transcriptionally.
- miR-29a overexpression suppressed NSCLC cell proliferation, migration, and invasion, mimicking LASP1 knockdown.
- LASP1 overexpression counteracted the suppressive effects of miR-29a.
- Upregulation of miR-29a inhibited tumor growth in vivo and improved survival in a mouse model.
Conclusions:
- miR-29a exerts a suppressive role in NSCLC by targeting LASP1.
- The miR-29a/LASP1 axis is a critical regulator of NSCLC malignant phenotypes.
- The miR-29a/LASP1 pathway represents a promising therapeutic strategy for NSCLC.
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