SOX12 contributes to the activation of the JAK2/STAT3 pathway and malignant transformation of esophageal squamous cell carcinoma

Li,Chunguang; Zhu,Maoling; Zhu,Ji; Lu,Qijue; Shi,Bowen; Sun,Bin; Chen,Hezhong

doi:10.3892/or.2020.7863

SOX12 contributes to the activation of the JAK2/STAT3 pathway and malignant transformation of esophageal squamous cell carcinoma

Authors:
- Chunguang Li
- Maoling Zhu
- Ji Zhu
- Qijue Lu
- Bowen Shi
- Bin Sun
- Hezhong Chen
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Affiliations: Department of Thoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200438, P.R. China, Department of Gastroenterology, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, P.R. China, Molecular Oncology Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
Published online on: November 19, 2020 https://doi.org/10.3892/or.2020.7863
Pages: 129-138
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As a crucial transcription factor, sex‑determining region Y box 12 (SOX12) is closely related with tumorigenesis and malignant transformation in various malignant tumor types. To date, the specific function of SOX12 in esophageal squamous cell carcinoma (ESCC) has remained largely elusive and requires further investigation. The present study aimed to determine whether aberrant expression of SOX12 is associated with malignant development of ESCC. The expression level of SOX12 in ESCC cells and tissues was analyzed by RT‑qPCR and western blotting. Short hairpin RNA (shRNA) targeting SOX12 was transfected into ESCC cells to knock down the expression of SOX12. Colony formation and Transwell assays were used to detect viability and mobility of ESCC cells. Signaling pathway‑related proteins were assessed using western blot analysis and cellular immunofluorescence. Clinical prognosis data was analyzed by Kaplan‑Meier and Cox logistic regression. The present results revealed that SOX12 was overexpressed in ESCC cells and tissues. Knockdown of the expression of SOX12 by shRNA inhibited the colony forming efficiency, migration and invasion capacities of ESCC cells in vitro. Recombinant protein of SOX12 could restore the aggressive phenotype of ESCC cells. Furthermore, knockdown of the expression of SOX12 inhibited the activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway by decreasing the expression of the JAK2/STAT3 signaling pathway. Recombinant protein of SOX12 could recover the activation of the JAK2/STAT3 signaling pathway. Analysis of the clinical data revealed that overexpression of SOX12 indicated shorter overall survival time (OS; P=0.0341) and disease‑free survival time (DFS; P=0.04). Univariate and multivariate analysis revealed that overexpression of SOX12 was an independent factor for ESCC. In conclusion, SOX12 was revealed to serve a crucial function in sustaining the viability, as well as enhancing the motility of ESCC cells via activating the JAK2/STAT3 signaling pathway. Thus, SOX12 may potentially serve as a novel biomarker and candidate for the targeted treatment of ESCC.

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