SPIN1 is a proto-oncogene and SPIN3 is a tumor suppressor in human seminoma
Damian Mikolaj Janecki1, Marcin Sajek1, Maciej Jerzy Smialek1
1Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Abstract:
SPIN1 is necessary for normal meiotic progression in mammals. It is overexpressed in human ovarian cancers and some cancer cell lines. Here, we examined the functional significance and regulation of SPIN1 and SPIN3 in the TCam-2 human seminoma cell line. We found that while SPIN1 overexpression reduced apoptosis in these cells, SPIN3 overexpression induced it. Similarly, SPIN1 upregulated and SPIN3 downregulated CYCD1, which is a downstream target of the PI3K/AKT pathway and contributes to apoptosis resistance in cancer cell lines. It appears that SPIN1 is pro-oncogenic and SPIN3 acts as a tumor suppressor in TCam-2 cells. To our knowledge, this is the first report of SPIN3 tumor suppressor activity. However, both SPIN1 and SPIN3 stimulated cell cycle progression. In addition, using luciferase reporters carrying SPIN1 or SPIN3 mRNA 3'UTRs, we found that PUM1 and PUM2 targeted and repressed SPINs. We also found that PUM1 itself strongly stimulated apoptosis and moderately slowed cell cycle progression in TCam-2 cells, suggesting that PUM1, like SPIN3, is a tumor suppressor. Our findings suggest that acting, at least in part, through SPIN1 and SPIN3, PUM proteins contribute to a mechanism promoting normal human male germ cell apoptotic status and thus preventing cancer.
Insights
SPIN1 promotes cancer, while SPIN3 suppresses it in human seminoma cells. PUM proteins, acting through SPIN1 and SPIN3, help prevent cancer by promoting germ cell apoptosis.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- SPIN1 is crucial for mammalian meiotic progression and is overexpressed in human ovarian cancers.
- The roles of SPIN1 and SPIN3 in cancer, particularly in male germ cell tumors, are not well understood.
Purpose of the Study:
- To investigate the functional significance and regulation of SPIN1 and SPIN3 in the TCam-2 human seminoma cell line.
- To determine the oncogenic or tumor-suppressive potential of SPIN1 and SPIN3.
- To identify regulatory mechanisms controlling SPIN1 and SPIN3 expression.
Main Methods:
- Utilized the TCam-2 human seminoma cell line for experiments.
- Assessed apoptosis and cell cycle progression following SPIN1 and SPIN3 overexpression.
- Quantified CYCD1 expression, a downstream target of the PI3K/AKT pathway.
- Employed luciferase reporter assays to study the regulation of SPIN1 and SPIN3 by PUM1 and PUM2.
Main Results:
- SPIN1 overexpression reduced apoptosis and upregulated CYCD1, indicating a pro-oncogenic role.
- SPIN3 overexpression induced apoptosis and downregulated CYCD1, suggesting a tumor suppressor function.
- Both SPIN1 and SPIN3 stimulated cell cycle progression.
- PUM1 and PUM2 were identified as repressors of SPIN1 and SPIN3.
- PUM1 demonstrated tumor suppressor activity by promoting apoptosis and slowing cell cycle progression.
Conclusions:
- SPIN1 acts as an oncoprotein, while SPIN3 functions as a tumor suppressor in TCam-2 cells.
- PUM proteins, through regulation of SPIN1 and SPIN3, contribute to maintaining apoptosis in male germ cells, potentially preventing cancer.
- This study provides novel insights into the roles of SPIN proteins and PUM proteins in male germ cell cancer development.
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