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J Cell Biochem. 2019 Nov 13. doi: 10.1002/jcb.29545. [Epub ahead of print]

Oncogenic microRNA-765 promotes the growth and metastasis of breast carcinoma by directly targeting ING4.

Author information

1
Department of oncology, Chengyang people's Hospital, Qingdao, Shandong, China.
2
Department of Radiotherapy, Chengyang people's Hospital, Qingdao, Shandong, China.
3
Department of Thyroid Breast Surgery, Chengyang people's Hospital, Qingdao, Shandong, China.

Abstract

Previous investigations have proved that microRNA (miR)-765 is significantly overexpressed in multiple tumor types. Nevertheless, the underlying molecular mechanism of miR-765 in mediating breast carcinoma cell growth and metastasis remains unclear. Quantitative real-time polymerase chain reaction was used to determine the levels of miR-765 and inhibitor of growth 4 (ING4) in breast carcinoma tissues and breast carcinoma cells. Cell proliferation, colony formation, wound healing, and Transwell invasion assays were used to analysis the role of miR-765 on breast carcinoma cell growth and aggressiveness. The expressions of ING4 were determined using Western blot analysis and immunohistochemical staining. The direct target of ING4 and miR-765 was confirmed using the luciferase reporter assay. Nude mice were subcutaneously implanted with miR-765 inhibitor transfected MDA-MB-231 cells to determine the potential role of miR-765 in tumor growth in vivo. We observed that miR-765 is overexpressed in breast carcinoma tissue and breast cancer cells. By using luciferase reporter gene bioassay, we find that ING4 is the direct target of miR-765 in breast carcinoma. The level of ING4 is inversely associated with the level of miR-765. The gain-of-function and loss-of-function experiments in vitro indicate that the downregulation of miR-765 suppresses the growth, mobility, and invasion abilities of breast cancer cells by inhibiting ING4. In addition, overexpression of ING4 suppresses the aggressiveness of the MDA-BA-231 cell that is induced by miR-761 in vitro. In this study, we prove that miR-765 regulates the growth and metastasis of breast cancer via modulating miR-765-ING4-negative feedback loop.

KEYWORDS:

Breast cancer; ING4; Invasion; Migration; miR-765

PMID:
31724215
DOI:
10.1002/jcb.29545

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