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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR‑133a suppresses cell proliferation, migration and invasion in human lung cancer by targeting MMP‑14
1Department of Oncology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
Abstract:
Lung cancer is the leading cause of cancer‑related mortality worldwide. Over half of lung cancer cases are diagnosed after metastasis, for which the median survival time is approximately 8 months. microRNAs (miRNAs), which are a class of single‑stranded endogenous non‑coding RNAs, are likely to be involved in most biological processes. miR‑133 plays roles in cardiac development and disease, and recent studies showed that miR‑133 is downregulated in various human malignancies, such as bladder and lung cancer. However, its detailed role in the processes of cancer remains to be determined. In the present study, we found that in the lung cancer cell lines A549 and NCI‑H1299 overexpression of miR‑133a suppressed cell proliferation, migration and invasion. The miR‑133a‑induced suppression of cell migration and invasion can be reversed by miR‑133a‑specific inhibitor. According to the mRNA sequence, matrix metalloproteinase (MMP)‑14, which is an important regulator of metastasis, is a predicted target of miR‑133a. This was confirmed by dual luciferase reporter assay. Moreover, miR‑133a overexpression decreases the mRNA and protein levels of MMP‑14. Collectively, these results suggest that miR‑133a may inhibit lung cancer metastasis by targeting MMP‑14 and may be used as an anti‑metastatic therapy in lung cancer patients.
Insights
MicroRNA 133a (miR-133a) suppresses lung cancer cell growth and metastasis. This study shows miR-133a targets matrix metalloproteinase-14 (MMP-14), offering potential anti-metastatic therapy for lung cancer.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Lung cancer is a leading cause of cancer mortality, often diagnosed at a metastatic stage.
- MicroRNAs (miRNAs) are non-coding RNAs involved in biological processes, with miR-133 implicated in various cancers.
- The specific role of miR-133 in lung cancer progression requires further elucidation.
Purpose of the Study:
- To investigate the function of miR-133a in lung cancer.
- To identify the molecular targets of miR-133a in lung cancer cells.
- To explore the potential of miR-133a as an anti-metastatic therapeutic agent.
Main Methods:
- Overexpression of miR-133a in A549 and NCI-H1299 lung cancer cell lines.
- Assessment of cell proliferation, migration, and invasion.
- Dual luciferase reporter assay to validate MMP-14 as a miR-133a target.
- Analysis of MMP-14 mRNA and protein levels.
Main Results:
- Overexpression of miR-133a significantly suppressed lung cancer cell proliferation, migration, and invasion.
- The inhibitory effects of miR-133a were reversible with a specific inhibitor.
- Matrix metalloproteinase-14 (MMP-14) was confirmed as a direct target of miR-133a.
- miR-133a overexpression led to decreased MMP-14 mRNA and protein levels.
Conclusions:
- miR-133a acts as a tumor suppressor in lung cancer by inhibiting cell proliferation, migration, and invasion.
- miR-133a exerts its anti-metastatic effects, at least in part, by targeting MMP-14.
- miR-133a holds promise as a potential therapeutic strategy against lung cancer metastasis.
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