Here, we examined Sox12 as a novel CSC marker in HCC
Here, we examined Sox12 as a novel CSC marker in HCC. (C), after serial adoptive transplantation. *p < 0.05. N = 20. Conversation In the current study, we analyzed Sox12 as a novel CSC marker for HCC. Our approach was theoretically supported by 2 recent studies. In the first study, Huang et al. showed that Sox12 upregulation was significantly correlated with loss of tumor encapsulation, microvascular invasion, and an advanced malignancy stage in human HCC patients (Huang et al., 2015). Mechanistically, they showed evidence to demonstrate that forkhead box Q1 directly binds to the Sox12 promoter and then trans-activates its expression, to induce epithelial-mesenchymal transition (EMT) through direct targets for Sox12, Twist1 and FGFBP1 (Huang et al., 2015). Since Twist (Matsuo et al., 2009; Yang et al., 2009; Zhang et al., 2012; 2015) and FGFBP1 (Ray et al., 2014; Yang et al., 2014; Zhu et al., 2016) are important regulators for tumor invasion, angiogenesis and metastasis, Sox12 may be expected to contribute to the invasive manner for CSC cells in HCC. In another study, Jiang et al. showed that a tumor suppressive microRNA, miR-874, was downregulated in HCC tissue, resulting in the augmentation of Sox12 levels through loss of a direct binding-mediated translational control (Jiang et al., 2017). In a previous study, Sox12 was found to be a direct promoter for HCC cell migration, invasion, and EMT (Jiang et al., 2017). Thus, the contribution of Sox12 to the HCC cell stemness may Diosmin be primarily on cell invasive manner, suggesting that combination of another CSC marker, which functions through cell cycle control on self-renewal, with Sox12, may be further improve the purification of CSC-like cells in HCC. This hypothesis may be tested in future study. Here, we used 2 lentiviruses to co-transduce the HCC cells. Although one cell may be only infected by one computer virus but not the other, we think that this possibility should be low, since the 2 viruses are of same type and comparable structure (Cockrell and Kafri, 2007; Houghton et Diosmin al., 2015; McCarron et al., 2016). A MOI of 100 further rendered this possibility even lower. Moreover, the absence of RFP+GFP? cells after viral contamination did not support this possibility. Furthermore, our isolation of GFP+ cells, regardless of RFP positivity, made the influence of this possibility to the interpretation of the data very limited. Together, the technique used in the current study should be validated. We selected two human HCC lines in this study, since they were commonly used HCC lines, but processed different malignancy. Analysis on both lines increased the reliability of the study and the results may be more relevant to main HCC. Indeed, previous studies have shown the association of Sox12 upregulation was an independent and significant risk factor for recurrence and reduced survival after curative resection (Huang et al., 2015). Studies on more clinical HCC specimens may increase our confidence of Sox12 as a clinic-relevant CSC marker. Recommendations Armstrong L., Stojkovic M., Dimmick I., Ahmad S., Stojkovic P., Hole N., Lako M. Phenotypic characterization of murine primitive hematopoietic progenitor cells isolated on basis of aldehyde dehydrogenase activity. Stem Cells. 2004;22:1142C1151. [PubMed] [Google Scholar]Brower V. Sorafenib plus cisplatin for hepatocellular carcinoma. Lancet Oncol. 2016;17:e424. [PubMed] [Google Scholar]Chiba T., Iwama A., Yokosuka O. Malignancy stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology. Hepatol Res. 2016;46:50C57. [PubMed] [Google Scholar]Cockrell A.S., Kafri T. Gene delivery by lentivirus vectors. Mol Biotechnol. 2007;36:184C204. [PubMed] [Google Scholar]Duester G. Families of retinoid dehydrogenases regulating vitamin A function: production of visual pigment and retinoic acid. Eur J Biochem. 2000;267:4315C4324. [PubMed] [Google Scholar]Dy P., Penzo-Mendez Rabbit Polyclonal to OR11H1 A., Wang H., Pedraza C.E., Macklin W.B., Lefebvre V. The three SoxC Diosmin proteins–Sox4, Sox11 and Sox12–exhibit overlapping expression patterns and molecular properties. Nucleic Acids Res. 2008;36:3101C3117. [PMC free article] [PubMed] [Google Scholar]Fang D.D., Kim Y.J., Lee C.N., Aggarwal S., McKinnon K., Mesmer D., Norton J., Birse Diosmin C.E., He T., Ruben S.M., et al. Growth of CD133(+) colon cancer cultures retaining stem cell properties to enable malignancy stem cell target discovery. Br J Malignancy. 2010;102:1265C1275. [PMC free article] [PubMed] [Google Scholar]Hess D.A., Meyerrose T.E., Wirthlin L., Craft T.P., Herrbrich P.E., Creer M.H., Nolta J.A. Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde.