microRNAs-107 inhibited autophagy, proliferation, and migration of breast cancer cells by targeting HMGB1

J Cell Biochem. 2019 May;120(5):8696-8705. doi: 10.1002/jcb.28157. Epub 2018 Dec 2.

Abstract

Purpose: To investigate the effects of microRNAs-107 (miR-107) on autophagy, proliferation, and migration of breast cancer cells and its mechanism by targeting high mobility group protein B1 (HMGB1).

Methods: Real-time polymerase chain reaction assay was used to detect the expression of miR-107 in breast cancer and its cell lines. In MDA-MB-231 and MDA-MB-453 breast cancer cells, the expression of p62, Beclin1 protein, and the changes of cell proliferation and migration after overexpression of m miR-107 were detected by Western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and transwell assays. Target Scan online prediction, dual luciferase reporter gene, and Western blot were used to verify the targeting relationship between miR-107 and HMGB1. The effects of silencing HMGB1 expression on p62, Beclin1 protein expression, cell proliferation, and migration ability were detected. The transfected MDA-MB-453 cells were inoculated into the right axilla of the nude mice, the tumor volume and weight were weighed, and the expression of miR-107, HMGB1, p62, and Beclin1 in the tumor were detected.

Results: The expression of miR-107 was downregulated in breast cancer tissues and cell lines (P < 0.01). The expression of p62 protein was upregulated (P < 0.01), while Beclin1 protein was downregulated (P < 0.01) and cell proliferation and migration ability were decreased (P < 0.01) after overexpressing miR-107 in MDA-MB-231 and MDA-MB-453 cells. The results of TargetScan online prediction, dual luciferase reporter gene, and Western blot showed that miR-107 could regulate HMGB1 expression. The expression of p62 protein was upregulated (P < 0.01), while Beclin1 protein was downregulated (P < 0.01) and cell proliferation and migration ability were decreased (P < 0.01) after silencing HMGB1 in MDA-MB-231 and MDA-MB-453 cells. The results of xenograft experiments showed that miR-107 could delay tumor growth and inhibit autophagy.

Conclusion: miR-107 could inhibit cell autophagy, proliferation, and migration of breast cancer cells by targeting HMGB1.

Keywords: autophagy; breast cancer; high mobility group protein B1; miR-107.