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Published on: June 12, 2019
MicroRNA-495 induces breast cancer cell migration by targeting JAM-A
Minghui Cao1, Weiwei Nie, Jing Li
1State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
Abstract:
MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression. The deregulated expression of miRNAs is associated with a variety of diseases, including breast cancer. In the present study, we found that miR-495 was markedly up-regulated in clinical breast cancer samples by quantitative real time-PCR (qRT-PCR). Junctional adhesion molecule A (JAM-A) was predicted to be a potential target of miR-495 by bioinformatics analysis and was subsequently verified by luciferase assay and Western blotting. JAM-A was found to be negatively correlated with the migration of breast cancer cells through loss-of-function and gain-of-function assays, and the inhibition of JAM-A by miR-495 promoted the migration of MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of JAM-A could restore miR-495-induced breast cancer cell migration. Taken together, our findings suggest that miR-495 could facilitate breast cancer progression through the repression of JAM-A, making this miRNA a potential therapeutic target.
Insights
MicroRNAs (miRNAs) promote breast cancer progression by downregulating Junctional Adhesion Molecule A (JAM-A). This study identifies miR-495 as a key factor in cancer cell migration, suggesting it as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are crucial post-transcriptional regulators implicated in various diseases, including breast cancer.
- Aberrant miRNA expression is a hallmark of cancer, driving tumorigenesis and progression.
- Understanding specific miRNA roles is vital for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the role of miR-495 in breast cancer.
- To identify the downstream targets of miR-495.
- To elucidate the mechanism by which miR-495 influences breast cancer cell migration.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for miRNA expression analysis in clinical samples.
- Bioinformatics analysis to predict miRNA targets.
- Luciferase assays and Western blotting to validate target interactions.
- Loss-of-function and gain-of-function assays to assess cell migration.
- Overexpression studies to confirm functional rescue.
Main Results:
- miR-495 was significantly upregulated in clinical breast cancer samples.
- Junctional Adhesion Molecule A (JAM-A) was identified as a direct target of miR-495.
- miR-495 inhibition of JAM-A promoted breast cancer cell migration (MCF-7 and MDA-MB-231 cells).
- Restoration of JAM-A expression reversed the pro-migratory effects induced by miR-495.
Conclusions:
- miR-495 facilitates breast cancer progression by repressing JAM-A expression.
- The miR-495/JAM-A axis plays a critical role in regulating cancer cell migration.
- miR-495 emerges as a potential therapeutic target for breast cancer treatment.
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