OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor.
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.
Asadi
Malek H
MH
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Mowla
Seyed J
SJ
Fathi
Fardin
F
Aleyasin
Ahmad
A
Asadzadeh
Jamshid
J
Atlasi
Yaser
Y
D000230:Adenocarcinoma / Q000235:genetics; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D050814:Octamer Transcription Factor-3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053148:Caspase 3; D053179:Caspase 7