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Published on: January 11, 2019
Altered expression of apoptotic genes in response to OCT4B1 suppression in human tumor cell lines
Mohammad Reza Mirzaei1, Ali Najafi, Mohammad Kazemi Arababadi
1Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Abstract:
OCT4B1 is a newly discovered spliced variant of OCT4 which is primarily expressed in pluripotent and tumor cells. Based on our previous studies, OCT4B1 is significantly overexpressed in tumors, where it endows an anti-apoptotic property to tumor cells. However, the mechanism by which OCT4B1 regulates the apoptotic pathway is not yet elucidated. Here, we investigated the effects of OCT4B1 suppression on the expression alteration of 84 genes involved in apoptotic pathway. The AGS (gastric adenocarcinoma), 5637 (bladder tumor), and U-87MG (brain tumor) cell lines were transfected with OCT4B1 or irrelevant siRNAs. The expression level of apoptotic genes was then quantified using a human apoptosis panel-PCR kit. Our data revealed an almost similar pattern of alteration in the expression profile of apoptotic genes in all three studied cell lines, following OCT4B1 suppression. In general, the expression of more than 54 apoptotic genes (64 % of arrayed genes) showed significant changes. Among these, some up-regulated (CIDEA, CIDEB, TNFRSF1A, TNFRSF21, TNFRSF11B, TNFRSF10B, and CASP7) and down-regulated (BCL2, BCL2L11, TP73, TP53, BAD, TRAF3, TRAF2, BRAF, BNIP3L, BFAR, and BAX) genes had on average more than tenfold gene expression alteration in all three examined cell lines. With some minor exceptions, suppression of OCT4B1 caused upregulation of pro-apoptotic and down-regulation of anti-apoptotic genes in transfected tumor cells. Uncovering OCT4B1 down-stream targets could further elucidate its part in tumorigenesis, and could lead to finding a new approach to combat cancer, based on targeting OCT4B1.
Insights
The study reveals that suppressing OCT4B1, a gene overexpressed in tumors, alters apoptotic gene expression. This suppression upregulates pro-apoptotic genes and downregulates anti-apoptotic genes in cancer cells, suggesting OCT4B1 as a potential cancer therapeutic target.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- OCT4B1 is a spliced variant of OCT4, predominantly found in pluripotent and tumor cells.
- OCT4B1 overexpression in tumors confers anti-apoptotic properties, but its regulatory mechanism remains unclear.
- Understanding OCT4B1's role in apoptosis is crucial for developing novel cancer therapies.
Purpose of the Study:
- To investigate the impact of OCT4B1 suppression on the expression of genes within the apoptotic pathway.
- To identify specific apoptotic genes regulated by OCT4B1 in various cancer cell lines.
- To elucidate the mechanism by which OCT4B1 influences tumor cell survival.
Main Methods:
- Utilized siRNA to suppress OCT4B1 expression in AGS, 5637, and U-87MG cancer cell lines.
- Quantified the expression levels of 84 apoptosis-related genes using a human apoptosis panel-PCR kit.
- Analyzed gene expression alterations across different tumor cell types to identify common patterns.
Main Results:
- OCT4B1 suppression led to significant expression changes in over 54% of the investigated apoptotic genes across all tested cell lines.
- Key pro-apoptotic genes (e.g., CASP7, TNFRSF1A) were upregulated, while anti-apoptotic genes (e.g., BCL2, BAX) were downregulated.
- The observed gene expression pattern indicated a shift towards apoptosis induction upon OCT4B1 knockdown.
Conclusions:
- OCT4B1 suppression effectively modulates the apoptotic pathway in tumor cells.
- Targeting OCT4B1 could reverse the anti-apoptotic effect in cancer cells, promoting cell death.
- Identifying OCT4B1 downstream targets offers a promising avenue for developing new anti-cancer strategies.
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