OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor

Abstract

The octamer-binding transcription factor 4 (OCT4) is involved in regulating pluripotency and self-renewal maintenance of embryonic stem cells. Recently, misexpression of OCT4 has been also reported in some adult stem as well as cancer cells; a finding which is still controversial. In addition to the previously described spliced variants of the gene (e.g., OCT4A and OCT4B), we have recently identified a novel variant of the gene, designated as OCT4-B1. In this study, we investigated a potential expression and function of OCT4B1 in a series of gastric cancer tissues and a gastric adenocarcinoma cell line, AGS. Using the Taqman real-time PCR approach, we have detected the expression of OCT4B1 in tumors with no or much lower expression in marginal samples of the same patients (p < 0.002). We have also analyzed the effects of OCT4B1 knock-down in AGS cell line treated with specific siRNA directed toward OCT4B1. Our data revealed that interfering with the expression of OCT4B1 caused profound changes in the morphology and cell cycle distribution of the cells. Furthermore, down-regulation of OCT4B1 significantly elevated the relative activity of caspase-3/caspase-7 and the rate of apoptosis in the cells (more than 30%). All together, our findings suggest that OCT4B1 has a potential role in tumorigenesis of gastric cancer and candidates the variant as a new tumor marker with potential value in diagnosis and treatment of gastric cancer.On the basis of the cancer stem cell (CSC) hypothesis, a subpopulation of cells within tumors is responsible for the sustained growth and propagation of tumors. CSCs are also believed to be the main reason for the tumor relapse and resistance to therapy. These cells share various characteristics with normal tissue-specific adult stem cells, including selfrenewal potential. Based on this hypothesis, CSCs are originating either from the dysregulated self-renewal control in normal adult stem cells or through reprogramming of the somatic progenitor or differentiated cells within the tissue. [1][2][3][4][5] The octamer-binding transcription factor 4 (OCT4, also known as OCT3 and POU5F1) belongs to a family of transcription factors containing the POU DNA-binding domain. The encoded protein acts as a master self-renewal regulator in embryonic stem cells and plays a critical role in maintaining the pluripotent state of stem cells. OCT4 expression is strongly repressed following stem cell differentiation. 6-10 Several recent studies have demonstrated the unexpected expression of the OCT4 gene in some human cancer cell lines and tissues, 11-18 including gastric cancer. 19 The human OCT4 gene can potentially encode three spliced variants, designated as OCT4A, OCT4B and the newly discovered OCTB1. 20,21 OCT4A is primarily localized within the nucleus of the embryonic stem cells, where it sustains the selfrenewal and pluripotency properties of the cells. In contrast, OCT4B is mainly located within the cytoplasm of somatic cancer cell lines and apparently lacks any self-renewal regulatory role. 21,22 In ...

An oncofetal and developmental perspective on testicular germ cell cancer

“…Investigations of OCT3/4 expression and protein availability are hampered by the presence of similar transcripts with different or complimentary functions, e.g. non-protein coding pseudogenes (n = 5) [206,214,229,230], anti-sense transcribed pseudogenes [231] and splice-variants (OCT4A: pluripotency, OCT4B: stress responseOCT4B1: possibly both) [208,214,[232][233][234][235][236][237]. In addition, translation of OCT3/4 is mediated by micro-RNAs, specifically miR-145 [238,239] and miR34a [240].…”

OCT3/4 expression is correlated with the invasion of gastric carcinoma

“…The expression level of OCT3/4 may predict the malignant potential of gastric cancer, and downregulation of its expression may suppress the cell invasion ability. Asadi et al (21) found that a novel spliced variant of OCT4 designated as OCT4B1 was highly expressed in a gastric cancer cell strain, and that downregulation of its expression accelerated cell apoptosis. The study also described OCT4B1 as a novel tumor marker with potential value in the diagnosis and treatment of gastric cancer.…”

Inducible pluripotent stem cells for the treatment of ischemic stroke: current status and problems

“…When iPSCs are transplanted into the ischemic brain, Klf4, c-Myc, Oct4 and Sox2, the four reprogramming factors to produce iPSCs, show strong expression in iPSC-derived tumors , indicating their highly relevant role in tumorigenicity. This hypotheses can be explained by the oncogene property of those factors, whereby MYC is a well-established oncogene (Ruggero, 2009;Albihn et al, 2010) and the other three transcription factors are also known to be highly expressed in various types of cancer (Sholl et al, 2010;Tian et al, 2010;Asadi et al, 2011). These genes have been found to be associated with tumor progression and a poor prognosis in specific types of cancer (Schoenhals et al, 2009).…”