SIRPB1 promotes prostate cancer cell proliferation via Akt activation

Song, Qiong1,2,3,4; Qin, Siyuan1,2,3; Pascal, Laura E.4; Zou, Chunlin1,2,3; Wang, Wenchu1,2,3; Tong, Haibo1,2,3; Zhang, Jian5; Catalona, William J.6; Dhir, Rajiv7; Morrell, Megan7; Balasubramani, Goundappa K.8; Lu, Yi1,2,3,5; Wang, Zhou4,7,9,10

2020-03

10.1002/pros.23950

PROSTATE   影响因子和分区

0270-4137

1097-0045

Background Signal regulatory protein beta 1 (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.

Akt signaling C4-2 FISH PC3 prostate cancer qPCR SIRPB1

SCI

英语

通讯

Enhancement Foundation for Young Teachers in Guangxi Universities[2019KY0132]

Endocrinology & Metabolism ; Urology & Nephrology

Endocrinology & Metabolism ; Urology & Nephrology

WOS:000508714000006

WILEY

CLINICAL MEDICINE

Web of Science

1.Guangxi Med Univ, Ctr Translat Med, Nanning, Guangxi, Peoples R China
2.Guangxi Med Univ, Sch Preclin Med, Nanning, Guangxi, Peoples R China
3.Minist Educ, Key Lab Longev & Ageing Related Dis, Nanning, Guangxi, Peoples R China
4.Univ Pittsburgh, Sch Med, Dept Urol, 5200 Ctr Ave,Suite G40, Pittsburgh, PA 15232 USA
5.Southern Univ Sci & Technol, Sch Med, 1088 Xueyuan Blvd, Shenzhen 518055, Guangdong, Peoples R China
6.Northwestern Univ, Dept Urol, Feinberg Sch Med, Chicago, IL 60611 USA
7.Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA
8.Univ Pittsburgh, Dept Epidemiol, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA
9.Univ Pittsburgh, Sch Med, Canc Inst, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA
10.Univ Pittsburgh, Sch Med, Canc Inst, Pittsburgh, PA USA

Song, Qiong,Qin, Siyuan,Pascal, Laura E.,et al. SIRPB1 promotes prostate cancer cell proliferation via Akt activation[J]. PROSTATE,2020,80(4):352-364.

Song, Qiong.,Qin, Siyuan.,Pascal, Laura E..,Zou, Chunlin.,Wang, Wenchu.,...&Wang, Zhou.(2020).SIRPB1 promotes prostate cancer cell proliferation via Akt activation.PROSTATE,80(4),352-364.

Song, Qiong,et al."SIRPB1 promotes prostate cancer cell proliferation via Akt activation".PROSTATE 80.4(2020):352-364.