miR-186-ANXA9 signaling inhibits tumorigenesis in breast cancer

Zhongrui Wang; Xiqian Zhou; Xiaochong Deng; Danrong Ye; Diya Liu; Baian Zhou; Wenfang Zheng; Xuehui Wang; Yuying Wang; Oyungerel Borkhuu; Lin Fang

doi:10.3389/fonc.2023.1166666

miR-186-ANXA9 signaling inhibits tumorigenesis in breast cancer

Front Oncol. 2023 Sep 29:13:1166666. doi: 10.3389/fonc.2023.1166666. eCollection 2023.

Authors

Zhongrui Wang^{1

2}, Xiqian Zhou³, Xiaochong Deng³, Danrong Ye³, Diya Liu³, Baian Zhou³, Wenfang Zheng³, Xuehui Wang³, Yuying Wang³, Oyungerel Borkhuu³, Lin Fang^{1

3}

Affiliations

¹ Department of Thyroid and Breast Surgery, Shanghai Tenth People's Hospital, Shanghai Tenth People's Hospital of Nanjing Medical University, Shanghai, China.
² Department of Breast and Thyroid Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
³ Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

Breast cancer (BC) ranks as the highest incidence among cancer types in women all over the world. MicroRNAs (miRNAs) are a class of short endogenous non-coding RNA in cells mostly functioning to silence the target mRNAs. In the current study, a miRNA screening analysis identified miR-186-5p to be downregulated in human breast cancer tumors. Functional studies in vitro demonstrated that overexpression of miR-186-5p inhibited cellular proliferation and induced cell apoptosis in multiple breast cancer cell lines including MDA-MB-231, MCF-7, and BT549 cells. Transplantation of the miR-186-5p-overexpressing MDA-MB-231 cells into nude mice significantly inhibited mammary tumor growth in vivo. Sequence blast analysis predicted annexin A9 (ANXA9) as a target gene of miR-186-5p, which was validated by luciferase reporter assay, QRT-PCR analysis, and western blot. Additional gene expression analysis of clinical tumor samples indicated a negative correlation between miR-186-5p and ANXA9 in human breast cancer. Knockdown of ANXA9 mimicked the phenotype of miR-186-5p overexpression. Reintroduction of ANXA9 back rescued the miR-186-5p-induced cell apoptosis. In addition, miR-186-5p decreased the expression of Bcl-2 and increased the expression of p53, suggesting a mechanism regulating miR-186-5p-induced cellular apoptosis. In summary, our study is the first to demonstrate miR-186-5p-ANXA9 signaling in suppressing human breast cancer. It provided a potential therapeutic target in breast cancer.

Keywords: ANXA9; apoptosis; breast cancer; cell proliferation; miR-186-5p.

Grants and funding

This work was supported by Grant No. 201640097 from the Shanghai Municipal Health Bureau of Shanghai, China (to LF), Grant No. YNCR2B008 from the Clinical Research Center of Shanghai Tenth People’s Hospital (to LF), Grant No. 82172240 from the National Natural Science Foundation of China (to LF).