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MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer.

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.

SUBMITTER: Lu Y

PROVIDER: S-EPMC5668497 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer.

Lu Y Y Qin T T Li J J Wang L L Zhang Q Q Jiang Z Z Mao J J

Cancer gene therapy 20170728 9

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 ...[more]

PMID: 28752859

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Project description:Studies performed in the last two decades have identified microRNA (miR)-1298-5p to display tumor-suppressive functions in several types of malignancy. In addition, the regulatory role of E2F transcription factor 1 (E2F1) has been reported in multiple types of cancer, including breast cancer (BC). However, whether miR-1298-5p participates in BC progression and whether a regulatory association exists between miR-1298-5p and E2F1 remains to be explored. The present study aimed to determine the role of miR-1298-5p and its interaction with E2F1 in BC. The expression of miR-1298-5p and E2F1 was examined by reverse transcription-quantitative PCR and western blot assays. The viability and proliferative capacity of BC cells were evaluated by Cell Counting Kit-8 and 5-bromo-2'-deoxyuridine assays, respectively. The apoptotic rate was assessed by the caspase-3 activity assay and flow cytometry; the protein expression levels of vimentin and E-cadherin were evaluated by western blotting. In addition, the adhesive and migratory abilities of BC cells were determined by conducting cell adhesion and wound healing assay, respectively. The target relationship between miR-1298-5p and E2F1 was validated by the luciferase reporter assay. The results of the present study revealed that the levels of miR-1298-5p were downregulated in BC tissues and cells compared with those in normal breast tissues and cells, respectively. In addition, miR-1298-5p was demonstrated to inhibit the proliferation, adhesion and migration of BC cells and to promote BC cell apoptosis. E2F1 was verified as a target gene of miR-1298-5p using the luciferase reporter assay. Additionally, E2F1 exhibited an opposite expression pattern compared with that of miR-1298-5p in BC tissues. Furthermore, the downregulation of miR-1298-5p in BC cells was reversed by silencing E2F1. Overall, the results of the present study suggested that miR-1298-5p repressed BC cell proliferation, adhesion and migration, and enhanced BC cell apoptosis by downregulating E2F1.

Dataset Information

MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer.

Publications

MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer.

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