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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-29a functions as a potential tumor suppressor through directly targeting CDC42 in non-small cell lung cancer
Yongqiang Li1, Zhi Wang2, Yijiang Li2
1Department of Emergency, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710038, P.R. China.
Abstract:
The expression and function of microRNA-29a (miR-29a) have been investigated in various types of cancer. In the present study, the expression, function and underlying molecular mechanism of miR-29a were investigated in non-small cell lung cancer (NSCLC). The expression level of miR-29a in NSCLC was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration and invasion ability were determined using Cell Counting Kit-8, cell migration and invasion assays, respectively. Bioinformatics analysis and dual-luciferase reporter assays were performed to determine whether cell division cycle 42 (CDC42) is a direct target gene of miR-29a. To assess CDC42 mRNA and protein expression following transfection with miR-29a, RT-qPCR and western blotting were performed. Following knockdown of CDC42, functional assays were performed to investigate the roles of CDC42 in NSCLC. The results demonstrated that miR-29a was downregulated in NSCLC and the decreased expression level of miR-29a was significantly associated with advanced tumor-node-metastasis classification and metastasis. In addition, upregulation of miR-29a inhibited cell proliferation, migration and invasion in NSCLC, whereas downregulation of miR-29a had the opposite effects. Furthermore, CDC42 was identified as a direct target gene of miR-29a in vitro. miR-29a was demonstrated to function as a tumor suppressor in NSCLC by directly targeting CDC42 and may be investigated further as a target therapy for NSCLC.
Insights
MicroRNA-29a (miR-29a) is downregulated in non-small cell lung cancer (NSCLC), inhibiting tumor suppressor activity. Restoring miR-29a levels suppresses NSCLC progression by targeting cell division cycle 42 (CDC42).
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNA-29a (miR-29a) dysregulation is implicated in various cancers.
- Its role in non-small cell lung cancer (NSCLC) requires further elucidation.
Purpose of the Study:
- To investigate the expression, function, and molecular mechanism of miR-29a in NSCLC.
- To determine if cell division cycle 42 (CDC42) is a direct target of miR-29a.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for miR-29a and CDC42 mRNA expression.
- Cell Counting Kit-8, migration, and invasion assays for proliferation, migration, and invasion.
- Bioinformatics analysis and dual-luciferase reporter assays to confirm CDC42 as a miR-29a target.
- Western blotting for CDC42 protein expression.
Main Results:
- miR-29a was significantly downregulated in NSCLC, correlating with advanced tumor stage and metastasis.
- Overexpression of miR-29a inhibited NSCLC cell proliferation, migration, and invasion.
- CDC42 was validated as a direct target of miR-29a.
- Knockdown of CDC42 partially mimicked the tumor-suppressive effects of miR-29a.
Conclusions:
- miR-29a acts as a tumor suppressor in NSCLC by directly targeting CDC42.
- miR-29a warrants further investigation as a potential therapeutic target for NSCLC.
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