OCT4B regulates p53 and p16 pathway genes to prevent apoptosis of breast cancer cells

Abstract

Octamer-binding transcription factor 4 (OCT4) is a transcription factor with a well-defined role in stem cell pluripotency. Two OCT4 isoforms, OCT4A and OCT4B, tend to be downregulated as normal cells differentiate. However, OCT4, particularly OCT4B, may become reactivated in cancer cells. Despite this observation, the exact function of OCT4B re-expression in cancer is unclear. In the present study, the role of OCT4 in breast cancer cells was determined. In particular, the ability of OCT4 to regulate key genes involved in cellular proliferation and apoptosis, two pathways that are frequently deregulated in cancer, was examined. The cyclin-dependent kinase inhibitor 2A locus encodes p16INK4a and p14ARF, two important cell cycle inhibitors. The tumor suppressor p53 also has well characterized roles in suppressing proliferation and promoting apoptosis. The present study demonstrated, via overexpression and genetic knockdown techniques, that OCT4B regulates the expression of several of these genes and ultimately regulates the rate of apoptosis of MCF-7 breast cancer cells. It was also observed that, while OCT4B and OCT4A regulate one another, it is OCT4B that serves a more prominent role in regulating the transcription of downstream genes. Taken together, the present results suggest that OCT4B is re-expressed in a number of breast cancer cell lines, where it affects both the transcription of cell cycle genes and the rate of apoptosis. These properties of OCT4B may depend on, at least in part, the co-function of OCT4A.

Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L

“…2A ). This observation could be explained by a regulatory impact of specific Oct4 isoforms on the expression of other transcript variants, as it was already shown for Oct4 A and B [ 41 ]. Furthermore, siRNAs employed in this experiment can potentially target non-spliced premature mRNA, affecting all splice variants.…”

Retinol/inflammation affect stemness and differentiation potential of gingival stem/progenitor cells via Wnt/β‐catenin

“…Although Nanog and Oct4 genes have two variants, Nanog1 and Nanog2 as well as Oct4A and Oct4B, respectively, Nanog1 and Nanog2 transcription variants were shown to be functionally equivalent in activating specific stem cell functions . In the event of the use of a non‐specifically designed POU5F1 primer for the investigation of the Oct4 mRNA expression, no differentiation between the two Oct4 variants, Oct4A (related to pluripotency) and Oct4B (related to somatic cellular activities, cell cycle regulation and apoptosis prevention), could be undertaken, as they both show a great similarity in their base pair sequence. Finally, in contrast to an earlier report, in the present study, retinol stimulation diminished Sox2 expression in the G‐MSCs, which could be ascribed to the divergence in cellular sources and their characteristic responses, as well as the difference in retinol concentrations between both studies.…”

“…event of the use of a non-specifically designed POU5F1 primer for the investigation of the Oct4 mRNA expression, no differentiation between the two Oct4 variants, Oct4A (related to pluripotency) and Oct4B (related to somatic cellular activities, cell cycle regulation and apoptosis prevention),39,40 could be undertaken, as they both show a great similarity in their base pair sequence. Finally, in contrast to an earlier report,41 in the present study, retinol stimulation diminished Sox2 expression in the G-MSCs, which could be ascribed to the divergence in cellular sources and their characteristic responses, as well as the difference in retinol concentrations between both studies.The primary stage of any periodontal regenerative/reparative approach remains to be cellular proliferation to obtain sufficient cellular amounts for the subsequent stages of cellular migration/ homing and functional differentiation.…”

Impacts of NF1 Gene Mutations and Genetic Modifiers in Neurofibromatosis Type 1

“…As for modifiers, ANRIL is especially relevant to the PNF number ( 28 ). It affects the expression of CDKN2A/ARF and CDKN2B tumor-suppressor genes, which further interrupts the cell cycle and apoptosis in PNF and other cancers ( 28 , 70 – 72 ). A study from Li et al underlines the important role of Runx1, functioning paradoxically either as a tumor-suppressor gene or as a dominant oncogene in NF1 neurofibroma initiation.…”