STARD4 promotes breast cancer cell malignancy

Zhang,Min; Xiang,Zhen; Wang,Feng; Shan,Rong; Li,Ling; Chen,Juan; Liu,Bao‑An; Huang,Juan; Sun,Lun‑Quan; Zhou,Wei‑Bing

doi:10.3892/or.2020.7802

STARD4 promotes breast cancer cell malignancy

Authors:
- Min Zhang
- Zhen Xiang
- Feng Wang
- Rong Shan
- Ling Li
- Juan Chen
- Bao‑An Liu
- Juan Huang
- Lun‑Quan Sun
- Wei‑Bing Zhou
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Affiliations: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Hunan Province Clinic Meditech Research Center for Breast Cancer, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: October 12, 2020 https://doi.org/10.3892/or.2020.7802
Pages: 2487-2502
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer (BRCA) is one of the most common malignancies encountered in women worldwide. Lipid metabolism has been found to be involved in cancer progression. Steroidogenic acute regulatory protein‑related lipid transfer 4 (STARD4) is an important cholesterol transporter involved in the regulatory mechanism of intracellular cholesterol homeostasis. However, to the best of our knowledge, the molecular functions of STARD4 in BRCA are unclear. Immunohistochemical staining and public dataset analysis were performed to investigate the expression levels of STARD4 in BRCA. In the present study, high expression of STARD4 was identified in BRCA samples and higher STARD4 expression was significantly associated with shorter distant metastasis‑free survival time in patients with BRCA, which indicated that STARD4 may be associated with BRCA progression. Cell cytometry system Celigo® analysis, Cell Counting K‑8 assays, flow cytometry, wound healing assays and transwell assays were used to investigate the effects of STARD4 knockdown on proliferation, cell cycle, apoptosis and migration in BRCA cells. Loss‑of‑function assays demonstrated that STARD4 acted as an oncogene to promote proliferation and cell cycle progression, while suppressing apoptosis in BRCA cells in vitro and in vivo. Furthermore, knockdown of STARD4 significantly suppressed BRCA metastasis. To assess the mechanism of action of STARD4, microarray analysis was performed following STARD4 knockdown in MDA‑MB‑231 cells. The data were analyzed in detail using bioinformatics, and a series of genes, including E74 like ETS transcription factor 1, cAMP responsive element binding protein 1 and p21 (RAC1) activated kinase 2, which have been previously reported to be crucial genes implicated in the malignant phenotype of cancer cells, were identified to be regulated by STARD4. Loss‑of function assays demonstrated that knockdown of STARD4 suppressed BRCA proliferation and migration. These findings suggested that STARD4 had an oncogenic effect in human BRCA progression.

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