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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer
1Teaching Laboratory of Morphology, Dalian Medical University, Dalian, China.
Abstract:
MicroRNAs (miRNAs) have been proven to be involved in cell metastasis and angiogenesis by interaction with the target mRNAs. Evidence has been confirmed that miR-140-5p is a tumor suppressor in human cancers such as breast cancer. However, the potential molecular mechanism of miR-140-5p in breast cancer invasion and angiogenesis is still poorly understood. According to our study, we reported that miR-140-5p inhibited the tumor invasion and angiogenesis of breast cancer cells both in vitro and in vivo by targeting VEGF-A. The mRNA amount of miR-140-5p was decreased in the breast cancer clinical samples and breast cancer with metastasis compared with the corresponding adjacent normal tissues and cancer without metastasis. MiR-140-5p mimics and a negative control were transfected into human MCF-7 and MDA-MB-231 cells. Transwell chambers were used to detect the invasive ability of the cells, and the angiogenic ability was assessed by tube-formation assay. The markers of invasion and angiogenesis, VEGF-A, CD31 and MMP-9, were detected by using immunohistochemistry and western blot analysis in vivo. VEGF-A was verified as a possible target gene of miR-140-5p, and corroborated by dual-luciferase reporter and ELISA. Taken together, the study elucidates the molecular mechanisms by which miR-140-5p inhibits breast cancer metastasis and angiogenesis, and provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for breast cancer patients.
Insights
MicroRNA-140-5p acts as a tumor suppressor in breast cancer. This study shows miR-140-5p inhibits cancer invasion and angiogenesis by targeting VEGF-A, offering a potential new therapy.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) regulate gene expression and are implicated in cancer progression, including metastasis and angiogenesis.
- miR-140-5p has been identified as a tumor suppressor in various human cancers, but its specific role in breast cancer invasion and angiogenesis requires further elucidation.
Purpose of the Study:
- To investigate the molecular mechanism by which miR-140-5p affects breast cancer invasion and angiogenesis.
- To identify the direct target of miR-140-5p involved in these processes.
Main Methods:
- Quantitative analysis of miR-140-5p expression in breast cancer tissues.
- In vitro assays (Transwell invasion, tube formation) using miR-140-5p mimics in breast cancer cell lines (MCF-7, MDA-MB-231).
- In vivo validation using immunohistochemistry and Western blot to assess invasion and angiogenesis markers (VEGF-A, CD31, MMP-9), and dual-luciferase reporter assays to confirm target interaction.
Main Results:
- Decreased miR-140-5p mRNA levels were observed in metastatic breast cancer tissues compared to non-metastatic ones.
- Overexpression of miR-140-5p significantly inhibited breast cancer cell invasion and angiogenesis in vitro.
- VEGF-A was identified and validated as a direct target of miR-140-5p, with its expression reduced upon miR-140-5p mimic transfection.
Conclusions:
- miR-140-5p suppresses breast cancer invasion and angiogenesis by directly targeting VEGF-A.
- The findings reveal a novel molecular mechanism for miR-140-5p in breast cancer.
- This study provides a strong foundation for developing novel microRNA-based therapeutic strategies for breast cancer treatment.
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