SATB2 knockdown decreases hypoxia‑induced autophagy and stemness in oral squamous cell carcinoma

Dong,Weijie; Chen,Yawen; Qian,Naiying; Sima,Guoqi; Zhang,Jianming; Guo,Zhiqin; Wang,Changlin

doi:10.3892/ol.2020.11589

SATB2 knockdown decreases hypoxia‑induced autophagy and stemness in oral squamous cell carcinoma

Authors:
- Weijie Dong
- Yawen Chen
- Naiying Qian
- Guoqi Sima
- Jianming Zhang
- Zhiqin Guo
- Changlin Wang
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Affiliations: Department of Stomatology, The First Hospital of Jiaxing, Jiaxing, Zhejiang 314000, P.R. China, Department of Stomatology, Yancheng Hospital Affiliated to Medical School of Southeast University, Yancheng, Jiangsu 224001, P.R. China
Published online on: May 6, 2020 https://doi.org/10.3892/ol.2020.11589
Pages: 794-802
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increasing evidence has suggested that special AT-rich sequence-binding protein 2 (SATB2) may be involved in the progression of numerous types of human cancer; however, the biological function of SATB2 in oral squamous cell carcinoma (OSCC) occurrence and progression remains relatively unknown. The present study aimed to investigate the potential role of SATB2 in the regulation of biological characteristics of OSSC during hypoxia. The expression of SATB2 in SCC9 cells was knocked down using small interfering RNA. Western blotting was used to determine the protein expression levels of SATB2, autophagy‑related proteins microtubule‑associated protein light chain (LC)3‑I/II and Beclin‑1, and stemness markers such as Oct‑4 (POU class 5 homeobox 1), Sox‑2 (SRY‑box 2) and Nanog (nanog homeobox). Transmission electron microscopy and monodansylcadaverine staining were used to detect the presence of autophagosomes. Furthermore, the self‑renewal capacity of cells was analyzed using colony forming assays; the cell proliferative, migratory and invasive ability were evaluated using CCK‑8, wound healing and Transwell assays, respectively; and the cell cycle distribution and rate of apoptosis were detected using flow cytometry. The expression levels of SATB2, autophagy‑related proteins and stemness markers were significantly increased in SCC9 cells following hypoxic treatment. Meanwhile, the genetic knockdown of SATB2 inhibited hypoxia‑mediated autophagy by decreasing the expression levels of Beclin‑1, and preventing the conversion of LC3‑I to LC3‑II and the accumulation of autophagosomes. The knockdown of SATB2 also inhibited the hypoxia‑induced colony‑forming ability and the expression of stemness markers. Functionally, it also inhibited the proliferative, migratory and invasive abilities of SCC9 cells, while inducing apoptosis and cell cycle arrest under hypoxia. In conclusion, the present study suggested that SATB2 may function as an oncogene in OSCC cells, and targeting SATB2 may be a potential therapeutic strategy for the treatment of OSCC.

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