Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Zhongshan Hospital, Xiamen University, Building 6, No. 209, South Hubin Road, 361004, Xiamen, China.
Lab Invest. 2020 Nov;100(11):1400-1410. doi: 10.1038/s41374-020-0445-0. Epub 2020 May 27.
SRY (sex-determining region Y)-box 13 (Sox13), a member of group D of the SRY-related high mobility group (HMG) box (Sox) family, is a critical regulator of embryonic development and cartilage formation. Few studies have investigated the role of Sox13 in tumorigenesis. The present study reveals the clinical significance and biological function of Sox13 in hepatocellular carcinoma (HCC). First, the expression of Sox13 in HCC samples was evaluated by qRT-PCR and western blotting, and its association with clinicopathological features and prognosis was determined. We found that Sox13 expression was higher in tumor tissue than in paired nontumor tissue. The upregulation of Sox13 was associated with poor differentiation, metastasis, recurrence and poor overall, and tumor-free survival of HCC patients. The function of Sox13 on HCC cell migration and invasion was then assessed by Transwell assay, and the results demonstrated that Sox13 promoted HCC cell invasion, migration, and epithelial-to-mesenchymal transition (EMT). Notably, the invasion, migration, and EMT of HCC cells induced by Sox13 overexpression could be abolished by Twist1 depletion, and Sox13 was positively correlated with Twist1 at both the mRNA and protein levels. Mechanistically, we revealed that Sox13 activated Twist1 transcription and consequently upregulated Twist1 expression. Furthermore, Sox13 formed a heterodimer with Sox5, and this heterodimer functionally cooperated to enhance the transcriptional activity of Twist1. Our findings suggest that Sox13 serves as an oncogene in HCC, and might be a novel prognostic and therapeutic candidate.
性别决定区 Y 框 13（Sox13）是 SRY 相关高迁移率族盒（Sox）家族 D 组的成员，是胚胎发育和软骨形成的关键调节因子。很少有研究探讨 Sox13 在肿瘤发生中的作用。本研究揭示了 Sox13 在肝细胞癌（HCC）中的临床意义和生物学功能。首先，通过 qRT-PCR 和 Western blot 评估 Sox13 在 HCC 样本中的表达，并确定其与临床病理特征和预后的关系。我们发现 Sox13 在肿瘤组织中的表达高于配对的非肿瘤组织。Sox13 的上调与 HCC 患者的低分化、转移、复发和总体及无瘤生存率差相关。然后通过 Transwell 实验评估 Sox13 对 HCC 细胞迁移和侵袭的功能，结果表明 Sox13 促进 HCC 细胞侵袭、迁移和上皮间质转化（EMT）。值得注意的是，Sox13 过表达诱导的 HCC 细胞侵袭、迁移和 EMT 可以被 Twist1 耗竭所消除，并且 Sox13 在 mRNA 和蛋白水平上均与 Twist1 呈正相关。机制上，我们揭示 Sox13 激活 Twist1 转录，从而上调 Twist1 表达。此外，Sox13 与 Sox5 形成异二聚体，该异二聚体功能上协同增强 Twist1 的转录活性。我们的研究结果表明 Sox13 是 HCC 中的癌基因，可能是一种新的预后和治疗候选物。
