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.

Targeting of TLE3 by miR‑3677 in human breast cancer promotes cell proliferation, migration and invasion

“…One previous study has reported that miR-128 regulates glucose metabolism and cell proliferation in triple-negative BC (25). Lu et al (26) indicated that miR-140-5p was significantly downregulated in BC, and that it may suppress invasion and angiogenesis by targeting vascular endothelial growth factor A. miR-190 has been demonstrated to inhibit BC metastasis by regulating transforming growth factor-β-induced epithelial-mesenchymal transition (27). However, the underlying mechanism by which miR-3677 modulates BC carcinogenesis remains obscure.…”

Long noncoding RNA MALAT1 regulates HDAC4‐mediated proliferation and apoptosis via decoying of miR‐140‐5p in osteosarcoma cells

“…The reason why miR‐140‐5p was selected as a studying point in the present research was owe to the similar MREs it providing for both MALAT1 and HDAC4. As a member of miRNAs family, miR‐140‐5p is widely reported as a key regulator in many malignant tumors like non‐small‐cell lung cancer, gastric cancer, breast cancer, hypopharyngeal carcinoma and so on . Fang Z reported that miR‐140‐5p suppressed gastric cancer's proliferation, migration, and invasion ability by targeting regulation of YES proto‐oncogene 1(YES1) .…”

“…As a member of miRNAs family, miR-140-5p is widely reported as a key regulator in many malignant tumors like non-small-cell lung cancer, gastric cancer, breast cancer, hypopharyngeal carcinoma and so on. [48][49][50][51] Fang Z reported that miR-140-5p suppressed gastric cancer's proliferation, migration, and invasion ability by targeting regulation of YES proto-oncogene 1(YES1). 48 In the present study, we illustrated that miR-140-5p was one of the "bridges" between MALAT1 and HDAC4.…”

MiR‐577 suppresses epithelial‐mesenchymal transition and metastasis of breast cancer by targeting Rab25

“…MiR‐452 inhibits the migration and invasion of BC cells by directly targeting RAB11A . MiR‐140‐5p inhibits angiogenesis and invasion by targeting VEGF‐A in BC . Hence, miRNAs and target genes could comprise an intricate network and play critical roles in BC metastasis.…”