scholarly journals USP16 regulates castration-resistant prostate cancer cell proliferation by deubiquitinating and stablizing c-Myc

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jianchao Ge ◽  
Wandong Yu ◽  
Junhong Li ◽  
Hangbin Ma ◽  
Pengyu Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Gene Signature ◽  
Cell Counting ◽  
Normal Prostate ◽  
Immunohistochemistry Staining ◽  
Myc Gene

Abstract Background c-Myc, a well-established oncogene, plays an important role in the initiation and progression of various cancers, including prostate cancer. However, its mechanism in cancer cell remains largely unknown and whether there exist a deubiquitinase targeting c-Myc also remains elusive. Methods Bioinformatic analysis and shRNA screening methods were used to identify potential deubiquitinases that correlate with c-Myc gene signature. Cell proliferation and viability were measured by Cell-Counting-Kit 8 and colony formation assays. A mouse xenograft model of PC3 cells was established to confirm the function of USP16 in vivo. The interaction between USP16 and c-Myc protein was assessed by co-immunoprecipitation and protein co-localization assays. Immunohistochemistry staining was performed to detect the expression of USP16, Ki67, and c-Myc in xenograft tissues and clinical tumour tissues. Furthermore, the correlation between USP16 and c-Myc was confirmed by RNA sequencing. Results Functional analyses identified USP16, known as a deubiquitinase, was strongly correlated with the c-Myc gene signature. Depletion of USP16 was shown to significantly suppress the growth of PCa cells both in vitro and in vivo. Co-immunoprecipitation and ubiquitination assays confirmed that USP16 served as a novel deubiquitinase of c-Myc and overexpression of c-Myc significantly rescued the effects of USP16 disruption. Immunohistochemistry staining and RNA-seq tactics were further used to confirm the positive correlation between USP16 and c-Myc expression. Expression of USP16 in human PCa tissues was higher than that seen in normal prostate tissues and its high expression was found associated with poor prognosis. Conclusions USP16 serves as a novel deubiquitinase of c-Myc. Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo. USP16 regulates PCa cell proliferation by deubiquitinating and stabilizing c-Myc, making it a potential therapeutic candidate for the treatment of PCa.

scholarly journals USP16 Regulates Castration-Resistant Prostate Cancer Cell Proliferation by Deubiquitinating and Stablizing c-Myc

2020 ◽  
Author(s):  
Jianchao Ge ◽  
Wandong Yu ◽  
Junhong Li ◽  
Hangbin Ma ◽  
Pengyu Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Gene Signature ◽  
Cell Counting ◽  
Normal Prostate ◽  
Immunohistochemistry Staining ◽  
Myc Gene

Abstract Backgroundc-Myc, a well-established oncogene, plays an important role in the initiation and progression of various cancers, including prostate cancer. However, its mechanism in cancer cell remains largely unknown and whether there exist a deubiquitinase targeting c-Myc also remains elusive.MethodsBioinformatic analysis and shRNA screening methods were used to identify potential deubiquitinases that correlate with c-Myc gene signature. Cell proliferation and viability were measured by Cell-Counting-Kit 8 and colony formation assays. A mouse xenograft model of PC3 cells was established to confirm the function of USP16 in vivo. The interaction between USP16 and c-Myc protein was assessed by co-immunoprecipitation and protein co-localization assays. Immunohistochemistry staining was performed to detect the expression of USP16, Ki67, and c-Myc in xenograft tissues and clinical tumour tissues. Furthermore, the correlation between USP16 and c-Myc was confirmed by RNA sequencing.ResultsFunctional analyses identified USP16, known as a deubiquitinase, was strongly correlated with the c-Myc gene signature. Depletion of USP16 was shown to significantly suppress the growth of PCa cells both in vitro and in vivo. Co-immunoprecipitation and ubiquitination assays confirmed that USP16 served as a novel deubiquitinase of c-Myc and overexpression of c-Myc significantly rescued the effects of USP16 disruption. Immunohistochemistry staining and RNA-seq tactics were further used to confirm the positive correlation between USP16 and c-Myc expression. Expression of USP16 in human PCa tissues was higher than that seen in normal prostate tissues and its high expression was found associated with poor prognosis.ConclusionsUSP16 serves as a novel deubiquitinase of c-Myc. Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo. USP16 regulates PCa cell proliferation by deubiquitinating and stabilizing c-Myc, making it a potential therapeutic candidate for the treatment of PCa.

scholarly journals KLF5 Is Crucial for Androgen-AR Signaling to Transactivate Genes and Promote Cell Proliferation in Prostate Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 748 ◽  
Author(s):  
Juan Li ◽  
Baotong Zhang ◽  
Mingcheng Liu ◽  
Xing Fu ◽  
Xinpei Ci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Transcriptional Activity ◽  
Prostate Cancer Cells ◽  
Normal Prostate ◽  
Promote Cell Proliferation ◽  
Therapeutic Opportunity

Androgen/androgen receptor (AR) signaling drives both the normal prostate development and prostatic carcinogenesis, and patients with advanced prostate cancer often develop resistance to androgen deprivation therapy. The transcription factor Krüppel-like factor 5 (KLF5) also regulates both normal and cancerous development of the prostate. In this study, we tested whether and how KLF5 plays a role in the function of AR signaling in prostate cancer cells. We found that KLF5 is upregulated by androgen depending on AR in LNCaP and C4-2B cells. Silencing KLF5, in turn, reduced AR transcriptional activity and inhibited androgen-induced cell proliferation and tumor growth in vitro and in vivo. Mechanistically, KLF5 occupied the promoter of AR, and silencing KLF5 repressed AR transcription. In addition, KLF5 and AR physically interacted with each other to regulate the expression of multiple genes (e.g., MYC, CCND1 and PSA) to promote cell proliferation. These findings indicate that, while transcriptionally upregulated by AR signaling, KLF5 also regulates the expression and transcriptional activity of AR in androgen-sensitive prostate cancer cells. The KLF5-AR interaction could provide a therapeutic opportunity for the treatment of prostate cancer.

scholarly journals circITGA7 Acts as a miR-370-3p Sponge to Suppress the Proliferation of Prostate Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Gang Luo ◽  
Guohao Li ◽  
Zhihua Wan ◽  
Yuanjie Zhang ◽  
Dong Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Expression Profiles ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Loss Of Function

Prostate cancer (PCa) refers to one of the most common tumors in male’s genitourinary system. Emerging research has confirmed that circRNAs play an important role in the occurrence and development of tumors. However, the correlation between circular RNA circITGA7 and PCa still remains unclear. Here, the role of circITGA7 in PCa was explored and the underlying mechanism was investigated as well. The circRNA expression profiles in PCa and the paracancerous tissues were established by high-throughput sequencing. The expression levels of circITGA7 in PCa tissues and cells were detected by qRT-PCR. Cell Counting Kit-8, colony formation, EdU, and flow cytometry assays were used to detect the effects of circITGA7 on PCa cell proliferation. To further explore the underlying mechanisms, bioinformatics analysis on downstream target genes was carried out. RNA immunoprecipitation and dual-luciferase reporter assays were used to verify the direct relationship between miR-370-3p and circITGA7 or P21CIP1. The present results demonstrated that circITGA7 was downregulated in PCa tissues and cells. Gain- or loss-of-function assays showed that circITGA7 inhibited the proliferation of PCa cells in vivo and in vitro. Mechanically, circITGA7 served as a sponge for miR-370-3p, and miR-370-3p could target P21CIP1 in PCa cells. The inhibition of cell proliferation induced by circITGA7 could be reversed by transfecting miR-370-3p mimic. Collectively, our data indicated that circITGA7 played an important role in inhibiting tumor proliferation in PCa and might be a potential therapeutic target.

scholarly journals circITGA7 Acts As miR-370-3p Sponge to Suppress The Proliferation of Prostate Cancer

2021 ◽  
Author(s):  
Yonglian Guo ◽  
Guohao Li ◽  
Zhihua Wan ◽  
Yuanjie Zhang ◽  
Dong Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Expression Profiles ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Loss Of Function

Abstract Objective: Prostate cancer (PCa) refers to one of the most common tumors in male’s genitourinary system. Emerging research has confirmed that circRNAs play an important role in the occurrence and development of tumors. However, the correlation between circular RNA circITGA7 and PCa still remains unclear. Here, the role of circITGA7 in PCa was explored and the underlying mechanism was investigated as well.Methods: The circRNA expression profiles in PCa and the paracancerous tissues were established by high-throughput sequencing. The expression levels of circITGA7 in PCa tissues and cells were detected by qRT-PCR. Cell Counting Kit-8, colony formation, EdU and flow cytometry assays were used to detect the effects of circITGA7 on PCa cell proliferation. To further explore the underlying mechanisms, bioinformatics analysis on downstream target genes was carried out. RNA immunoprecipitation and dual-luciferase reporter assays were used to verify the direct relationship between miR-370-3p and circITGA7 or P21CIP1.Results: circITGA7 was downregulated in PCa tissues and cells. Gain- or loss-of-function assays showed that circITGA7 inhibited the proliferation of PCa cells in vivo and in vitro. Mechanically, circITGA7 served as a sponge for miR-370-3p and miR-370-3p could target P21CIP1 in PCa cells. The inhibition of cell proliferation induced by circITGA7 could be reversed by transfecting miR-370-3p mimic. Conclusion: Our data indicated that circITGA7 played an important role in inhibiting tumor proliferation in PCa and might be a potential therapeutic target.

scholarly journals CircLRP6 contributes to prostate cancer growth and metastasis by binding to miR-330-5p to up-regulate NRBP1

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Linghui Qin ◽  
Xiaosong Sun ◽  
Fei Zhou ◽  
Cheng Liu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Tumor Growth ◽  
Western Blot ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Mesenchymal Transition

Abstract Background Circular RNA low-density lipoprotein receptor-related protein 6 (circLRP6) is considered as an oncogene in many types of cancers. However, the function and mechanisms of circLRP6 in prostate cancer (PCa) tumorigenesis remain largely undefined. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were conducted to assess the expression of circLRP6, microRNA (miR)-330-5p, and nuclear receptor binding protein 1 (NRBP1). Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2’-deoxyuridine (EDU) incorporation, flow cytometry, transwell, wound healing, and western blot assays were performed to detect cell proliferation, apoptosis, and metastasis in vitro. Subcutaneous tumor growth was observed in nude mice to investigate the role of circLRP6 in vivo. The targeting relationship between miR-330-5p and NRBP1 or circLRP6 was verified using dual-luciferase reporter, pull-down, and RNA immunoprecipitation (RIP) assays. Immunohistochemistry was employed to test relative protein expression. Results CircLRP6 was highly expressed in PCa tissues and cells, knockdown of circLRP6 impaired PCa cell growth and metastasis in vitro by affecting cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT). Mechanistic studies showed that circLRP6 could competitively bind with miR-330-5p to prevent the degradation of its target gene NRBP1. Rescue assay suggested that miR-330-5p inhibition reversed the inhibitory effects of circLRP6 knockdown on PCa cell growth and metastasis. Moreover, overexpression of miR-330-5p suppressed PCa progression via NRBP1. Notably, tumor formation assay indicated that circLRP6 silencing impeded tumor growth and EMT in vivo. Conclusion Our findings demonstrated that circLRP6 promoted PCa tumorigenesis and metastasis through miR-330-5p/NRBP1 axis, suggesting a potential therapeutic target for PCa.

794: Valproic Acid Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth

scholarly journals Investigation of the In Vitro and In Vivo efficiency of RM-532-105, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, in LAPC-4 prostate cancer cell and tumor models

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0171871 ◽  
Author(s):  
Lucie Carolle Kenmogne ◽  
Jenny Roy ◽  
René Maltais ◽  
Mélanie Rouleau ◽  
Bertrand Neveu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Hydroxysteroid Dehydrogenase ◽  
Tumor Models ◽  
Type 3

scholarly journals PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Zhongwei Li ◽  
Diandian Wang ◽  
Xintian Chen ◽  
Wenwen Wang ◽  
Pengfei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Cycle Progression ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Ezh2 Expression

AbstractProtein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR342-EZH2) has a great effect on PRMT1-induced cell proliferation. We also demonstrate that meR342-EZH2 can accelerate breast cancer cell proliferation in vitro and in vivo. Further, we show that meR342-EZH2 promotes cell cycle progression by repressing P16 and P21 transcription expression. In terms of mechanism, we illustrate that meR342-EZH2 facilitates EZH2 binding with SUZ12 and PRC2 assembly by preventing AMPKα1-mediated phosphorylation of pT311-EZH2, which results in suppression of P16 and P21 transcription by enhancing EZH2 expression and H3K27me3 enrichment at P16 and P21 promoters. Finally, we validate that the expression of PRMT1 and meR342-EZH2 is negatively correlated with pT311-EZH2 expression. Our findings suggest that meR342-EZH2 may become a novel therapeutic target for the treatment of breast cancer.

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