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SIRPB1 promotes prostate cancer cell proliferation via Akt activation
Author(s) -
Song Qiong,
Qin Siyuan,
Pascal Laura E.,
Zou Chunlin,
Wang Wenchu,
Tong Haibo,
Zhang Jian,
Catalona William J.,
Dhir Rajiv,
Morrell Megan,
Balasubramani Goundappa K.,
Lu Yi,
Wang Zhou
Publication year - 2020
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23950
Subject(s) - prostate cancer , cancer research , cell cycle , biology , cell growth , carcinogenesis , gene knockdown , cyclin d1 , microbiology and biotechnology , protein kinase b , cell , cancer , signal transduction , apoptosis , biochemistry , genetics
Abstract Background Signal regulatory protein β1 (SIRPB1) is a signal regulatory protein member of the immunoglobulin superfamily and is capable of modulating receptor tyrosine kinase‐coupled signaling. Copy number variations at the SIRPB1 locus were previously reported to associate with prostate cancer aggressiveness in patients, however, the role of SIRPB1 in prostate carcinogenesis is unknown. Methods Fluorescence in situ hybridization and laser‐capture microdissection coupled with quantitative polymerase chain reaction was utilized to determine SIRPB1 gene amplification and messenger RNA expression in prostate cancer specimens. The effect of knockdown of SIRPB1 by RNA interference in PC3 prostate cancer cells on cell growth in colony formation assays and cell mobility in wound‐healing, transwell assays, and cell cycle analysis was determined. Overexpression of SIPRB1 in C4‐2 prostate cancer cells on cell migration, invasion, colony formation and cell cycle progression and tumor take rate in xenografts was also determined. Western blot assay of potential downstream SIRPB1 pathways was also performed. Results SIRPB1 gene amplification was detected in up to 37.5% of prostate cancer specimens based on in silico analysis of several publicly available datasets. SIRPB1 gene amplification and overexpression were detected in prostate cancer specimens. The knockdown of SIRPB1 significantly suppressed cell growth in colony formation assays and cell mobility. SIRPB1 knockdown also induced cell cycle arrest during the G 0 /G 1 phase and enhancement of apoptosis. Conversely, overexpression of SIPRB1 in C4‐2 prostate cancer cells significantly enhanced cell migration, invasion, colony formation, and cell cycle progression and increased C4‐2 xenograft tumor take rate in nude mice. Finally, this study presented evidence for SIRPB1 regulation of Akt phosphorylation and showed that Akt inhibition could abolish SIRPB1 stimulation of prostate cancer cell proliferation. Conclusions These results suggest that SIRPB1 is a potential oncogene capable of activating Akt signaling to stimulate prostate cancer proliferation and could be a biomarker for patients at risk of developing aggressive prostate cancer.