Dataset Information

Cullin-1 promotes cell proliferation via cell cycle regulation and is a novel in prostate cancer.

ABSTRACT:

Background

There is no reliable marker available for early detection, diagnostic confirmation, or disease prognosis available of prostate cancer (PCa). We aimed to evaluate the function of Cullin-1 and unravel its underlying molecular mechanism to develop novel treatment options equivalent to PCa.

Method

We used immunohistochemistry to analyze the correlation between Cullin-1 expression and clinicopathologic variables and patient survival. The Cullin-1 level was tested in PCa cells. The role of regulation of Cullin-1 in PCa was applied in vitro and vivo. In addition, we further investigated the signaling pathway of Cullin-1 in prostate cancer cell proliferation.

Result

We first discovered that Cullin-1 expression was upregulated in human PCa tissues and inversely related with PCa differentiation. We then found that high expression of Cullin-1 protein suggested a poor prognosis in PCa patients. Also, Cullin-1 promotes PCa cell proliferation in vitro and tumor growth in vivo. We then found that the mechanism of Cullin-1 regulation on cell-cycle progression is due to increased expression of p21 and p27, and decreased expression of cyclin D1 and cyclin E after Cullin-1 knockdown.

Conclusion

Cullin-1 exerts multiple biological effects in the PCa cell line. Through promoting proliferation and by countering cisplatin-induced apoptosis, Cullin-1 has been deeply implicated in the pathogenesis and development of PCa.

SUBMITTER: Jiang H

PROVIDER: S-EPMC4396298 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Cullin-1 promotes cell proliferation via cell cycle regulation and is a novel in prostate cancer.

Jiang Haowen H He Donghua D Xu Hua H Liu Jun J Qu Lianxi L Tong Shijun S

International journal of clinical and experimental pathology 20150201 2

<h4>Background</h4>There is no reliable marker available for early detection, diagnostic confirmation, or disease prognosis available of prostate cancer (PCa). We aimed to evaluate the function of Cullin-1 and unravel its underlying molecular mechanism to develop novel treatment options equivalent to PCa.<h4>Method</h4>We used immunohistochemistry to analyze the correlation between Cullin-1 expression and clinicopathologic variables and patient survival. The Cullin-1 level was tested in PCa cell ...[more]

PMID: 25973042

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Project description: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 G0 /G1 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.

Project description:BackgroundHistone deacetylases (HDACs) engage in the regulation of various cellular processes by controlling global gene expression. The dysregulation of HDACs leads to carcinogenesis, making HDACs ideal targets for cancer therapy. However, the use of HDAC inhibitors (HDACi) as single agents has been shown to have limited success in treating solid tumors in clinical studies. This study aimed to identify a novel downstream effector of HDACs to provide a potential target for combination therapy.MethodsTranscriptome sequencing and bioinformatics analysis were performed to screen for genes responsive to HDACi in breast cancer cells. The effects of HDACi on cell viability were detected using the MTT assay. The mRNA and protein levels of genes were determined by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The binding of CREB1 (cAMP-response element binding protein 1) to the promoter of the KDELR (The KDEL (Lys-Asp-Glu-Leu) receptor) gene was validated by the ChIP (chromatin immunoprecipitation assay). The association between KDELR2 and protein of centriole 5 (POC5) was detected by immunoprecipitation. A breast cancer-bearing mouse model was employed to analyze the effect of the HDAC3-KDELR2 axis on tumor growth.ResultsKDELR2 was identified as a novel target of HDAC3, and its aberrant expression indicated the poor prognosis of breast cancer patients. We found a strong correlation between the protein expression patterns of HADC3 and KDELR2 in tumor tissues from breast cancer patients. The results of the ChIP assay and qRT-PCR analysis validated that HDAC3 transactivated KDELR2 via CREB1. The HDAC3-KDELR2 axis accelerated the cell cycle progression of cancer cells by protecting the centrosomal protein POC5 from proteasomal degradation. Moreover, the HDAC3-KDELR2 axis promoted breast cancer cell proliferation and tumorigenesis in vitro and in vivo.ConclusionOur results uncovered a previously unappreciated function of KDELR2 in tumorigenesis, linking a critical Golgi-the endoplasmic reticulum traffic transport protein to HDAC-controlled cell cycle progression on the path of cancer development and thus revealing a potential therapeutical target for breast cancer.

Dataset Information

Cullin-1 promotes cell proliferation via cell cycle regulation and is a novel in prostate cancer.

Background

Method

Result

Conclusion

Publications

Cullin-1 promotes cell proliferation via cell cycle regulation and is a novel in prostate cancer.

Similar Datasets

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