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SOX5 Regulates Cell Proliferation, Apoptosis, Migration and Invasion in KSHV-Infected Cells

Abstract

Kaposi’s sarcoma (KS) originates from vascular endothelial cells, with KS-associated herpesvirus (KSHV) as the etiological agent. SRY-box transcription factor 5 (SOX5) plays different roles in various types of cancer, although its role in KS remains poorly understood. In this study, we identified the role of SOX5 in KS tissues and KSHV-infected cells and elucidated the molecular mechanism. Thirty-two KS patients were enrolled in this study. Measurement of SOX5 mRNA and protein levels in human KS tissues and adjacent control tissues revealed lower levels in KS tissues, with KS patients having higher SOX5 level in the early stages of the disease compared to the later stages. And SOX5 mRNA and protein was also lower in KSHV-infected cells (iSLK-219 and iSLK-BAC) than normal cells (iSLK-Puro). Additionally, SOX5 overexpression inhibited cell proliferation and promoted apoptosis and decreased KSHV-infected cell migration and invasion. Moreover, we found that SOX5 overexpression suppressed the epithelial-to-mesenchymal transition of KSHV-infected cells. These results suggest SOX5 is a suppressor factor during KS development and a potential target for KS treatment.

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Acknowledgements

We thank Prof. Ke Lan (State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China) for generously sharing iSLK-PURO, iSLK-219 and iSLK-BAC cell lines. This work was supported by the National Natural Science Foundation of China (U1603117; 81560473), Xinjiang Production and Construction Corps Key Areas Innovation Team Project (2018CB002) and a grant from Shihezi University International Cooperation Project (GJHZ201901).

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Contributions

YZ and JZ designed the experiments. WMY, YGF, MC, TL and JZ carried out the experiments. YEW, ZJS, and JZ acquired the clinical samples, YGF and WMY analyzed the data. WMY, YGF, JZ and YZ wrote the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jun Zheng or Yan Zeng.

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The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

All patients provided written informed consent, the procedures used were in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki), and the study was approved by the Ethics Committee of the First Affiliated Hospital of the Medical College, Shihezi University, and Xinjiang Uygur Autonomous Region Sixth People’s Hospital.

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Yuan, WM., Fan, YG., Cui, M. et al. SOX5 Regulates Cell Proliferation, Apoptosis, Migration and Invasion in KSHV-Infected Cells. Virol. Sin. 36, 449–457 (2021). https://doi.org/10.1007/s12250-020-00313-3

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  • DOI: https://doi.org/10.1007/s12250-020-00313-3

Keywords

  • SRY-box transcription factor 5 (SOX5)
  • Kaposi sarcoma (KS)
  • Proliferation
  • Apoptosis
  • Epithelial-to-mesenchymal transition (EMT)