SPIN1 is a proto-oncogene and SPIN3 is a tumor suppressor in human seminoma.

// Damian Mikolaj Janecki 1 , Marcin Sajek 1 , Maciej Jerzy Smialek 1 , Maciej Kotecki 1, 2 , Barbara Ginter-Matuszewska 1 , Bogna Kuczynska 1 , Anna Spik 1 , Tomasz Kolanowski 1, 3 , Riko Kitazawa 4 , Maciej Kurpisz 1 and Jadwiga Jaruzelska 1 1 Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland 2 Department of Developmental, Molecular and Chemical Biology, Tufts University Medical School, Boston, Massachusetts, U.S.A. 3 Institute of Pharmacology and Toxicology, Technische Universitat Dresden, Germany 4 Division of Molecular Pathology, Ehime University, Graduate School of Medicine, Shitsukawa, Toon City, Ehime, Japan Correspondence to: Jadwiga Jaruzelska, email: jadwiga.jaruzelska@igcz.poznan.pl Barbara Ginter-Matuszewska, email: bginter@man.poznan.pl Keywords: human seminoma; PUM proteins; testis germ cell tumors; SPIN1; SPIN3 Received: January 20, 2018      Accepted: July 31, 2018      Published: August 21, 2018 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.