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

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.

Chemotherapeutic Stress Influences Epithelial–Mesenchymal Transition and Stemness in Cancer Stem Cells of Triple-Negative Breast Cancer

“…The function of miRNAs during tumor growth and progression as well modulation of chemoresistance is diverse and complex. MiR-107 could induce or inhibit metastasis in different cancer types [24,25], while miR-200a-3p could influence different signaling pathways in hepatocellular carcinoma [29,30]. In the present study, we observed a similar or inversed regulation of six miRNAs in just two of the three BCSC lines considered.…”

Johnny on the Spot-Chronic Inflammation Is Driven by HMGB1

“…In breast cancer, miR-129-5p direct regulation of HMGB1 and consequently of autophagy contributes to ameliorate radiosensitivity in vitro (185). Additionally, even though the effects on chemosensitivity were not evaluated, miR107 was found to be downregulated in human breast tumors and cell lines (196). This miR targets HMGB1 directly and regulates its autophagy inducing properties in vitro , while overexpression reduces tumorigenesis in vivo .…”

Upregulation of miR-129-5p increases the sensitivity to Taxol through inhibiting HMGB1-mediated cell autophagy in breast cancer MCF-7 cells

“…High mobility group box 1 (HMGB1) is a regulator of autophagy as a ubiquitous nuclear protein, which can regulate and promote various DNA-related activities such as transcription, replication, and repair (28 –30). Recently, studies indicated that HMGB1 plays an essential role in chemotherapy sensitivity through modulating protective autophagy in a number of cancers, including breast cancer (31,32). Thus, targeting HMGB1-mediated autophagy might improve the chemosensitivity of cancer cells.…”