Abstract
ABSTRACTTestis expressed 10 (Tex10), a new core component of the pluripotency circuitry, has been reported to positively regulate embryonic stem cell (ESC) super-enhancers to promote ESC self-renewal; however, the expression and function of Tex10 in hepatocellular carcinoma (HCC) and liver cancer stem cells remains unclear. The present study was designed to investigate the expression patterns of Tex10 with immunohistochemistry, western blotting and RT-qPCR in samples from HCC patients and HCC cell lines. The results obtained show that Tex10 was highly expressed in HCC tissues, and elevated Tex10 protein levels positively correlate with the poorly differentiated carcinoma. Likewise, we found that Tex10 expression in the high-metastasis HCCLM3 potential cell line was higher than that in the low-metastasis HepG2 potential cell line, and Tex10 expression in liver cancer stem cells was also higher than that in adhered HCC cells. In addition, Tex10 knockdown decreased stem cell marker expression and drug resistance. Tex10 promoted cancer stemness through activation of the STAT3 signaling pathway. Taken together, our study demonstrates that Tex10 plays a potent carcinogenic role in HCC tumorigenesis by maintaining cancer stem cell properties through activation of the STAT3 signaling pathway and promoting chemo-resistance. Thus, targeting Tex10 may provide a novel and effective therapeutic strategy to suppress the tumorigenicity of advanced HCC.
Highlights
We found that Testis expressed 10 (Tex10) expression in the highmetastasis HCCLM3 potential cell line was higher than that in the low-metastasis HepG2 potential cell line, and Tex10 expression in liver cancer stem cells was higher than that in adhered hepatocellular carcinoma (HCC) cells
The expression of Tex10 was detected with immunohistochemical staining (IHC) in pairs of human normal liver tissues and HCC tissues, which were randomly chosen from six poorly-differentiated HCC patients who underwent surgical resection in the Nanchong Central Hosptial in Nanchong, China
The expression of Tex10 was negative (Figure 1(a)); Tex10 was detected in a nuclear location in cancerous tissue (Figure 1(b)), suggesting that Tex10 expression is up-regulated in HCC
Summary
Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and the third highest cause of cancer-related death in the world [1] .In China, approximately 366,000 new cases and 321,000 deaths occurred in 2012, the incidence of which ranks is in third place and the mortality of which ranks in second place for various cancers [2].HCC is an aggressive tumor usually diagnosed at a late stage and for which effective therapies remain lacking [3]. the treatment for HCC has been greatly improved, the mortality rate remains high because of drug resistance and recurrence [4].Cancer stem cells (CSCs) are a unique population of cancer cells that are responsible for tumor initiation, metastasis, selfrenewal and drug resistance [5,6].Several lines of evidence have suggested that drug resistance and recurrence of HCC are closely associated with the existence of CSCs [7,8]. The significance of Tex is manifested by the fact that as a new Sox2-interacting protein, Tex was identified as a key pluripotency factor that plays a crucial role in embryonic stem cell (ESC) self-renewal and pluripotency, early embryo development and reprogramming [11]. The key pluripotency transcription factor Nanog of ESCs contributes to facilitating formation of tumor-initiating stem-like cells in livers of mice [15,16]. Based on these findings, we propose a hypothesis that Tex may be relevant to the stem cells of HCC and participate in the development of HCC. The present study investigated the expression and biological function of Tex in HCC and liver CSCs
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