HORMAD1 promotes docetaxel resistance in triple negative breast cancer by enhancing DNA damage tolerance Corrigendum in /10.3892/or.2021.8146

Zong,Beige; Sun,Lu; Peng,Yang; Wang,Yihua; Yu,Yu; Lei,Jinwei; Zhang,Yingzi; Guo,Shipeng; Li,Kang; Liu,Shengchun

doi:10.3892/or.2021.8089

HORMAD1 promotes docetaxel resistance in triple negative breast cancer by enhancing DNA damage tolerance

Corrigendum in: /10.3892/or.2021.8146

Authors:
- Beige Zong
- Lu Sun
- Yang Peng
- Yihua Wang
- Yu Yu
- Jinwei Lei
- Yingzi Zhang
- Shipeng Guo
- Kang Li
- Shengchun Liu
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Affiliations: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, P.R. China, Department of Pathology, Chongqing Medical University, Chongqing 400015, P.R. China, Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: May 21, 2021 https://doi.org/10.3892/or.2021.8089
Article Number: 138
Copyright: © Zong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

HORMA domain‑containing protein 1 (HORMAD1), is normally expressed only in the germline, but is frequently re‑activated in human triple‑negative breast cancer (TNBC); however, its function in TNBC is largely unknown. In the present study, the expression and biological significance of HORMAD1 in human TNBC was evaluated. Bioinformatics analysis and reverse transcription‑quantitative PCR were used to evaluate HORMAD1 expression in datasets and cell lines. HORMAD1 protein expression was detected in TNBC samples using immunohistochemical assays, and the effect of HORMAD1 on cell proliferation was determined using Cell Counting Kit‑8, plate colony formation and standard growth curve assays. Cell cycle, reactive oxygen species (ROS) and apoptosis analyses were conducted using flow cytometry. The activity of caspases was measured using caspase activity assay kit. The levels of key apoptosis regulators and autophagy markers were detected by western blot analysis. TNBC cell survival and apoptosis were not influenced by small interfering RNA targeting HORMAD1 alone; however, HORMAD1 knockdown enhanced autophagy and docetaxel (Doc)‑induced apoptosis, compared with the control group. Furthermore, higher ROS levels and caspase‑3, ‑8 and ‑9 activity were detected in MDA‑MB‑436 TNBC cells with HORMAD1 knockdown upon exposure to Doc. The levels of the induced DNA damage marker γH2AX were also higher, while those of the DNA repair protein RAD51 were lower in TNBC cells with HORMAD1 knockdown compared with the controls. Furthermore, the expression of the autophagy marker P62 was enhanced in MDA‑MB‑231 cells in response to HORMAD1 overexpression. Notably, Doc‑induced apoptosis was similarly increased by both HORMAD1 overexpression and treatment with the autophagy inhibitor, 3‑methyladenine (3MA); however, the Doc‑induced increase in autophagy was not inhibited by 3MA. The present data indicated that HORMAD1 was involved in autophagy and that the inhibition of autophagy can partially enhance the induction of apoptosis by Doc. The role of HORMAD1 in the DNA damage tolerance of tumor cells may be the main reason for Doc resistance; hence, HORMAD1 could be an important therapeutic target in TNBC.

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