SOX5 Regulates Cell Proliferation, Apoptosis, Migration and Invasion in KSHV-Infected Cells
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RESEARCH ARTICLE
SOX5 Regulates Cell Proliferation, Apoptosis, Migration and Invasion in KSHV-Infected Cells Wu-Mei Yuan1,2 • Ya-Ge Fan2 • Meng Cui2 • Ting Luo2 • Ya-E Wang1 • Zhan-Jun Shu3 • Juan Zhao2 Jun Zheng1,2 • Yan Zeng2
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Received: 1 July 2020 / Accepted: 16 September 2020 Ó Wuhan Institute of Virology, CAS 2020
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. Keywords SRY-box transcription factor 5 (SOX5) Kaposi sarcoma (KS) Proliferation Apoptosis Epithelial-tomesenchymal transition (EMT)
Introduction Kaposi’s sarcoma (KS) is an invasive tumor of vascular endothelial cells and is possibly associated with KSassociated herpesvirus (KSHV; also identified as human herpesvirus-8). Four KS variants exist: classical KS (CKS), Wu-Mei Yuan and Ya-Ge Fan have contributed equally to this work. & Yan Zeng [email protected] & Jun Zheng [email protected] 1
Department of Stomatology, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832000, China
2
Key Laboratory of Xinjiang Endemic and Ethnic Disease and Department of Biochemistry, School of Medicine, Shihezi University, Shihezi 832000, China
3
AIDS Research Office, National Traditional Chinese Medicine Research Base in Xinjiang and the Sixth People’s Hospital of Xinjiang Uygur Autonomous Region, ¨ ru¨mqi 830000, China U
endemic KS, organ-transplant KS, and epidemic autoimmune deficiency syndrome-related KS (Boshoff and Weiss 2001; Cook-Mozaffari et al. 1998; Pelser et al. 2009). Typical skin lesions of CKS present in the lower and upper extremities and generally affect elderly men of Mediterranean or Eastern European origin (Jackson et al. 2016; Mesri et al. 2010). In China, it has been shown that the highest incidence of classic KS is found mostly among people of Uygur ethnicity in Xinjiang (Dilnur et al. 2001; Zheng et
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