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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-31-5p modulates cell cycle by targeting human mutL homolog 1 in human cancer cells
Zhiwei Zhong1, Zhuo Dong, Lihua Yang
1Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, China.
Abstract:
MicroRNAs (miRNAs) and DNA mismatch repair (MMR) have been linked to human cancer progression. Human mutL homolog 1 (hMLH1), one of the core MMR genes, defects in lung cancer development. However, the interaction between miRNAs and MMR genes and their regulatory effect on cell cycle remain poorly understood. In this study, we investigated the role of miR-31-5p in hMLH1 gene expression and the effect of miR-31-5p on cell cycle in non-small cell lung cancer (NSCLC). We found that miR-31-5p was inversely correlated with hMLH1 expression in NSCLC cell lines and hMLH1 was a direct target of miR-31-5p. Knockdown of miR-31-5p induced a cell cycle arrest at G2/M phase and increased hMLH1 protein expression in NSCLC cells. Conversely, overexpression of miR-31-5p significantly induced cell cycle arrest at S phase and decreased hMLH1 protein expression. Furthermore, knockdown of hMLH1 upregulated miR-31-5p expression and caused cell cycle arrest at S phase. Data from this study revealed that miR-31-5p modulates cell cycle by targeting hMLH1 protein at the posttranscriptional level in NSCLC, which may represent a novel therapy strategy for lung cancer by targeting miR-31-5p.
Insights
MicroRNAs (miRNAs) regulate cell cycle in lung cancer by targeting the hMLH1 DNA repair gene. Targeting miR-31-5p offers a potential new therapy for non-small cell lung cancer (NSCLC).
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) and DNA mismatch repair (MMR) genes, including human mutL homolog 1 (hMLH1), are implicated in human cancer progression.
- The specific roles of miRNAs in regulating MMR genes and their impact on the cell cycle in lung cancer remain unclear.
Purpose of the Study:
- To investigate the regulatory role of miR-31-5p in human mutL homolog 1 (hMLH1) gene expression.
- To determine the effect of miR-31-5p on the cell cycle in non-small cell lung cancer (NSCLC).
Main Methods:
- Analysis of miR-31-5p and hMLH1 expression correlation in NSCLC cell lines.
- Experimental manipulation (knockdown and overexpression) of miR-31-5p and hMLH1.
- Cell cycle phase analysis (G2/M and S phase arrest) using flow cytometry.
- Western blot analysis to assess protein expression levels.
Main Results:
- miR-31-5p expression was inversely correlated with hMLH1 expression in NSCLC cells, with hMLH1 identified as a direct target.
- miR-31-5p knockdown led to G2/M phase arrest and increased hMLH1 protein levels.
- miR-31-5p overexpression resulted in S phase arrest and decreased hMLH1 protein levels.
- hMLH1 knockdown upregulated miR-31-5p and induced S phase arrest.
Conclusions:
- miR-31-5p modulates the cell cycle in NSCLC by post-transcriptionally targeting hMLH1.
- This miR-31-5p/hMLH1 interaction represents a potential novel therapeutic strategy for lung cancer treatment.
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