Expression of HOXC10 gene regulates the growth and invasion of prostate cancer cells

The present study was undertaken to decipher the role of HOXC10 gene in regulating the growth and metastasis of prostate cancer. The results revealed significant (p<0.05) up-regulation of HOXC10 gene in human prostate cancer tissues and cell lines. The silencing of HOXC10 transcript level significantly (p<0.05) inhibited the growth and colony formation of DU145 and 22Rv1 prostate cancer cells. The DAPI staining revealed that inhibition of DU145 and 22Rv1 prostate cancer cell viability was due to the induction of apoptosis. The transwell assay showed that HOXC10 significantly (p<0.05) inhibits the invasion of prostate cancer cells. The Western blotting revealed that HOXC10 gene exerts its effects via modulation of Ras/Raf/MEK/ERK signaling cascade. Collectively, the results point towards the therapeutic potential of HOXC10 in the treatment of prostate cancer.

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Therapeutic Potential Role of miRNAs in Pancreatic and Prostate Cancer Cells

10.1201/9781003229650-11 ◽

2022 ◽

pp. 239-274

Author(s):

Loutfy H. Madkour

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Potential Role ◽

Therapeutic Potential ◽

Prostate Cancer Cells

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Roles of the Na+/H+ Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion

International Journal of Molecular Sciences ◽

10.3390/ijms222413263 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13263

Author(s):

Xiuju Li ◽

Benjamin Buckley ◽

Konstantin Stoletov ◽

Yang Jing ◽

Marie Ranson ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Cancer Cell ◽

Colony Formation ◽

Prostate Cancer Cell ◽

Cancer Cell Migration ◽

Prostate Cancer Cells

Prostate cancer is a leading cause of cancer-associated deaths in men over 60 years of age. Most patients are killed by tumor metastasis. Recent evidence has implicated a role of the tumor microenvironment and urokinase plasminogen activator (uPA) in cancer cell migration, invasion, and metastasis. Here, we examine the role of the Na+/H+ exchanger isoform 1 (NHE1) and uPA in DU 145 prostate cancer cell migration and colony formation. Knockout of NHE1 reduced cell migration. The effects of a series of novel NHE1/uPA hexamethylene-amiloride-based inhibitors with varying efficacy towards NHE1 and uPA were examined on prostate cancer cells. Inhibition of NHE1—alone, or with inhibitors combining NHE1 or uPA inhibition—generally did not prevent prostate cancer cell migration. However, uPA inhibition—but not NHE1 inhibition—prevented anchorage-dependent colony formation. Application of inhibitors at concentrations that only saturate uPA inhibition decreased tumor invasion in vivo. The results suggest that while knockout of NHE1 affects cell migration, these effects are not due to NHE1-dependent proton translocation. Additionally, while neither NHE1 nor uPA activity was critical in cell migration, only uPA activity appeared to be critical in anchorage-dependent colony formation of DU 145 prostate cancer cells and invasion in vivo.

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miRNA-214-5p inhibits prostate cancer cell proliferation by targeting SOX4

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02449-2 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Guangchi Xu ◽

Yin Meng ◽

Lihe Wang ◽

Bo Dong ◽

Feifei Peng ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Target Genes ◽

Prostate Cancer Cell ◽

Luciferase Reporter ◽

Prostate Cancer Cells ◽

Cancer Tissues

Abstract Background Prostate cancer is the most common malignant tumor in men. Due to the lack of theoretical research on its pathogenic mechanism, the current cure rate is still low. miRNAs play an important role in the pathogenesis of various cancers. miRNA-214-5p plays an important role in the development of a variety of cancers. This study aims to explore the expression level of miR-214-5p in prostate cancer and make a preliminary study of its molecular mechanism in the development of prostate cancer to provide effective new strategies for the treatment of prostate cancer. Methods The target genes of miRNA-214-5p were predicted with bioinformatics technology, and the target relationship between miRNA-214-5p and its target genes was verified with dual luciferase reporter assay. RT-qPCR and Western blot were used to detect the expression levels of miRNA-214-5p and target genes in 50 clinical samples and two common prostate continuous cell lines, respectively. The targeting relationship between miRNA-214-5p and its target genes was verified with clinical data. miRNA-214-5p and miRNA-214-5p inhibitor was over-expressed in DU-145 cell lines to verify the effect of miRNA-214-5p on prostate cancer cell proliferation and SOX4 gene expression. And the mechanism of miRNA-214-5p inhibiting the proliferation of prostate cancer cells were analyzed by detecting the expression difference of downstream factors of SOX4 pathway. Bioinformatics analysis showed that miRNA-214-5p combined with SOX4 3′UTR region, and dual luciferase reporter assay further verified the reliability of the predicted results. The low expression of miRNA-214-5p was observed in prostate cancer tissues and cells, while high expression of SOX4 was observed in prostate cancer tissues and cells. Results Overexpression of miRNA-214-5p to prostate cancer cells significantly inhibited the proliferation of cancer cells, and the expression of SOX4 was inhibited in the transfected cell line. After transfection of miRNA-214-5p inhibitor into prostate cancer cells, the cell proliferation rate further increased. Meanwhile, overexpression of miRNA-214-5p effectively inhibited the expression of SOX4 downstream factors, including c-Myc, eIF4E, and CDK4. However, the specific knockdown of SOX4 through SOX4 shRNA significantly reduced the proliferation of prostate cancer cell lines. Conclusions miRNA-214-5 can inhibit the proliferation of prostate cancer cells by specifically targeting S0X4 and inhibiting the expression of growth factors downstream of this pathway.

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Circular RNA circ_0057558 Controls Prostate Cancer Cell Proliferation Through Regulating miR-206/USP33/c-Myc Axis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.644397 ◽

2021 ◽

Vol 9 ◽

Author(s):

Tao Ding ◽

Yanjun Zhu ◽

Huimin Jin ◽

Ping Zhang ◽

Jianming Guo ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Negative Correlation ◽

Bioinformatics Analysis ◽

Prostate Cancer Cell ◽

Prostate Cancer Cells ◽

Cancer Tissues

We previously reported the elevated expression of circ_0057558 in prostate cancer tissues and cell lines. Here, we aimed to determine the biological function of circ_0057558 in prostate cancer. In the current study, circ_0057558 knockdown in prostate cancer cells significantly repressed cell proliferation and colony formation, but promoted cell arrest and enhanced the sensitivity to docetaxel. Bioinformatics analysis prediction and RNA-pull down assay identified miR-206 as the potential binding miRNA of circ_0057558. A negative correlation was observed between the expression of miR-206 and circ_0057558 in prostate cancer tissues. miR-206 mimics rescued the function of circ_0057558 overexpression on prostate cancer cells. Further, the bioinformatics analysis and luciferase assay suggested that miR-206 may target ubiquitin-specific peptidase 33 (USP33). USP33 mRNA expression has negative correlation with miR-206 expression and positive correlation with circ_0057558 expression in prostate cancer tissues. USP33 overexpression partially blocked the effects of miR-206 mimics on prostate cell proliferation. USP33 could bind and deubiquitinate c-Myc. Increased c-Myc protein by circ_0057558 overexpression was partially reversed by miR-206 mimics. The proliferation inhibition activity of MYC inhibitor 361 (MYCi361) was more prominent in primary prostate cancer cells and patient-derived xenograft (PDX) model with higher level of circ_0057558. Collectively, circ_0057558 gives an impetus to cell proliferation and cell cycle control in prostate cancer cell lines by sponging miR-206 and positively regulating the transcription of the miR-206 target gene USP33.

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Targeting the USP1 dependent KDM4A protein stability as a potential prostate cancer therapy

10.21203/rs.2.17158/v1 ◽

2019 ◽

Author(s):

Shu-Zhong Cui ◽

Ling-Ling Fan ◽

You-Qiang Li ◽

Xin-Yan Geng ◽

De-Xue Fu ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Survival ◽

Cancer Cells ◽

Real Time Pcr ◽

Therapeutic Target ◽

Knockout Mouse ◽

Prostate Cancer Cell ◽

Prostate Cancer Cells ◽

Anti Cancer

Abstract Background: Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death in American men. The histone demethylase KDM4A is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. The biological role and mechanism of KDM4A in regulating AR activity in prostate cancer, however, remain to be established. Methods: KDM4A expression in PTEN knockout mouse was determined using western blotting, Real-time PCR and immunohistochemical. Functional assays, such as cell survival, cell colony formation, anchorage-independent growth and a xenograft tumor model were used to determine the oncogenic role of KDM4A in prostate cancer cells. Association of KDM4A with USP1 and the deubiquitination assay were determined by co-immunoprecipitation, immunofluorescent staining and immunoblotting. USP1-KDM4A axis promotes AR-dependent c-Myc expression was further investigated using western blotting, chromatin immunoprecipitation and Real-time PCR. The specific USP1 inhibitor ML323 was used for assessing the role of USP1 in prostate cancer cell survival. Co-expression of KDM4A with USP1 was determined by immunohistochemical staining in 146 prostate cancer tissue samples. Results: Herein, we reported KDM4A expression was upregulation in PTEN knockout mouse prostate tissue. Depletion of KDM4A in prostate cancer cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of USP1-KDM4A/AR axis in driving prostate cancer cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression were observed in 70% of prostate tumors and inhibition of USP1 promotes prostate cancer cells response to therapeutic agent_enzalutamide. Our studies propose USP1 may be an anti-cancer therapeutic target in prostate cancer. Conclusions: Our findings demonstrate that USP1 deubiquitinates and stabilizes KDM4A, which promotes recruitment of AR to the c-Myc gene enhancer and highlight USP1 potential as an anti-cancer therapeutic target in prostate cancer. Keywords: USP1; Prostate cancer; KDM4A; Deubiquitination; Tumorigenesis

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The role of androgen receptor in glucose transporters expression in prostate cancer cells

Endocrine Abstracts ◽

10.1530/endoabs.37.gp.30.03 ◽

2015 ◽

Author(s):

Pedro Gonzalez-Menendez ◽

David Hevia ◽

Juan C Mayo ◽

Rosa M Sainz

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Cells ◽

Glucose Transporters ◽

Prostate Cancer Cells

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Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line

Scientific Reports ◽

10.1038/s41598-021-88519-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sukhneeraj P. Kaur ◽

Arti Verma ◽

Hee. K. Lee ◽

Lillie M. Barnett ◽

Payaningal R. Somanath ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Cancer Cells ◽

Cancer Cell ◽

Stromal Cell ◽

Prostate Cancer Cell ◽

Bone Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Prostate Cancer Cells

AbstractCancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.

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Distinct roles for the RNA-binding protein Staufen1 in prostate cancer

BMC Cancer ◽

10.1186/s12885-021-07844-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kristen A. Marcellus ◽

Tara E. Crawford Parks ◽

Shekoufeh Almasi ◽

Bernard J. Jasmin

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Rna Binding ◽

Prostate Cancer Cell ◽

Rna Binding Protein ◽

Migration And Invasion ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Prostate Cells

Abstract Background Prostate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients. Our previous work on the RNA-binding protein Staufen1 demonstrated its novel role in cancer biology, and in particular rhabdomyosarcoma tumorigenesis. To build upon this work, we have focused on the role of Staufen1 in other forms of cancer and describe here the novel and differential roles of Staufen1 in prostate cancer. Methods Using a cell-based approach, three independent prostate cancer cell lines with different characteristics were used to evaluate the expression of Staufen1 in human prostate cancer relative to control prostate cells. The functional impact of Staufen1 on several key oncogenic features of prostate cancer cells including proliferation, apoptosis, migration and invasion were systematically investigated. Results We show that Staufen1 levels are increased in all human prostate cancer cells examined in comparison to normal prostate epithelial cells. Furthermore, Staufen1 differentially regulates growth, migration, and invasion in the various prostate cancer cells assessed. In LNCaP prostate cancer cells, Staufen1 regulates cell proliferation through mTOR activation. Conversely, Staufen1 regulates migration and invasion of the highly invasive, bone metastatic-derived, PC3 prostate cells via the activation of focal adhesion kinase. Conclusions Collectively, these results show that Staufen1 has a direct impact in prostate cancer development and further demonstrate that its functions vary amongst the prostate cancer cell types. Accordingly, Staufen1 represents a novel target for the development of much-needed therapeutic strategies for prostate cancer.

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