OCT4B2, a novel alternative spliced variant of OCT4, is significantly upregulated under heat-stress condition and downregulated in differentiated cells

Tumour Biol. 2017 Oct;39(10):1010428317724280. doi: 10.1177/1010428317724280.

Abstract

OCT4 is a crucial transcription factor that maintains self-renewal and pluripotency of embryonic stem and embryonic carcinoma cells. The human OCT4 gene can generate at least three variants (OCT4A, OCT4B, and OCTB1) via alternative splicing and alternative promoters. It has been previously reported that OCT4A is the main isoform, retaining stemness state in embryonic stem and embryonic carcinoma cells. There are several reports on the expression of OCT4A, OCT4B, and OCT4B1 in some cancers and tumor cells. The expression of OCT4 in cancer tissues and cell lines appeared to be highly controversial since it was believed that OCT4 is exclusively expressed in embryonic stem/embryonic carcinoma cells. Here, we are reporting the detection of a novel alternatively spliced variant of OCT4, OCT4B2, in several pluripotent and tumor cell lines. Moreover, the expression pattern of OCT4B2 in the course of neural differentiation of NT2 and NCCIT, embryonic carcinoma cells, was similar to that of OCT4A. OCT4B2 was highly expressed in undifferentiated cells; however, its expression was sharply downregulated upon induction of differentiation. Overexpression of OCT4B2 did not affect the distribution of cells in different cell-cycle phases of transfected cells, compared to the mock transfected cells. Interestingly, the expression of OCT4B2 transcript was elevated under the heat-shock induction. In conclusion, we are reporting a new variant of OCT4, which is expressed under different physiological conditions. The finding shed more light on complexity of OCT4 expression and functions.

Keywords: OCT4A; OCT4B2; cancer; differentiation; heat-shock; stem cell.

MeSH terms

  • Alternative Splicing / genetics*
  • Cell Differentiation / genetics*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Octamer Transcription Factor-3 / biosynthesis*
  • Octamer Transcription Factor-3 / genetics
  • Pluripotent Stem Cells / metabolism

Substances

  • Octamer Transcription Factor-3
  • POU5F1 protein, human