1. Academic Validation
  2. Histocompatibility Minor 13 (HM13), targeted by miR-760, exerts oncogenic role in breast cancer by suppressing autophagy and activating PI3K-AKT-mTOR pathway

Histocompatibility Minor 13 (HM13), targeted by miR-760, exerts oncogenic role in breast cancer by suppressing autophagy and activating PI3K-AKT-mTOR pathway

  • Cell Death Dis. 2022 Sep 25;13(8):728. doi: 10.1038/s41419-022-05154-4.
Haiyan Yang  # 1 Zhi Li  # 2 Zhangwei Wang  # 1 Xu Zhang 1 Xinyuan Dai 1 Guoren Zhou 3 Qiang Ding 4
Affiliations

Affiliations

  • 1 Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, PR China.
  • 2 Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223399, PR China.
  • 3 Department of Oncology, Jiangsu Cancer Hospital & the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, 210009, PR China. zhouguoren888@njmu.edu.cn.
  • 4 Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, PR China. dingqiang@njmu.edu.cn.
  • # Contributed equally.
Abstract

Histocompatibility Minor 13 (HM13) is reported to participate in regulating multiple cancers. In the present study, we uncovered that HM13 was highly expressed in breast Cancer and correlated with worse prognosis. Downregulation of HM13 could suppress breast Cancer cell proliferation and metastasis abilities. Tumorigenicity mediated by HM13 was also observed in the xenograft model. Knockdown of HM13 could activate Autophagy by inducing endoplasmic reticulum (ER) stress. Moreover, further experiments demonstrated that downregulated HM13 could inhibit PI3K-AKT-mTOR pathway. We then verified that HM13 was a direct target of miR-760 functioned as a tumor -suppressor in breast Cancer. And the tumor suppressive effects of miR-760 could be partially reversed by HM13. Taken together, these findings elucidated that HM13, targeted by miR-760, could play an oncogenic role in breast Cancer by inducing autophagic inhibition and facilitating PI3K-AKT-mTOR pathway. Our findings suggested HM13 could act as a novel therapeutic target candidate for breast Cancer and supported the idea that Autophagy inducers might represent a new approach to treat breast Cancer.

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