scholarly journals MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration-resistant prostate cancer

Oncogene ◽  
2019 ◽  
Vol 38 (24) ◽  
pp. 4820-4834 ◽  
Author(s):  
Yicun Wang ◽  
Xin Li ◽  
Wei Liu ◽  
Bingjin Li ◽  
Dongquan Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Chromosome 8Q24

Statin inhibits the proliferation of human castration-resistant prostate cancer cells by controlling NFkB-LIN28B-let7 miRNA signaling pathway.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 269-269 ◽  
Author(s):  
Chang Wook Jeong ◽  
Ja Hyeon Ku ◽  
Hyeon Hoe Kim ◽  
Cheol Kwak ◽  
Minyong Kang
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Simvastatin Treatment ◽  
Castration Resistant

269 Background: Although statin use has been associated with improved outcomes in prostate cancer, the molecular mechanism of this action is still unclear. Based on previous findings, we aimed to investigate the potential role of NFkB-Lin28B-let7 miRNA signaling pathway in human prostate cancer, particularly, castration-resistant prostate cancer (CRPC) cells, as a molecular mechanism of statin effect. Methods: Various human CRPC cell lines (PC3, DU145, 22Rv1, C42B) were used in this study. Proliferation of prostate cancer cells were measured by MTT assay and colony formation assay. Lin28B and NF-κB expression were controlled by siRNA transfection and the expression on Lin28 and let-7 miRNA were quantitated using RT-PCR and western blotting. Results: Notably, simvastatin treatment on various CRPC cell lines decreased cell viabilities in a dose dependent manner. It also significantly inhibited cell growth in clonogenic assay. In these CRPC cells, LIN28 gene was highly expressed in mRNa and protein levels. Conversely, micro RNA (miRNA) expressions of let7 family were remarkably downregulated in CRPC cells. By simvastatin treatment, mRNA and protein level of Lin28B were decreased, while let7 miRNA expressions were restored, which was the key finding of the current study. Considering NFkB is the upstream molecule of Lin28B, we found that the double treatment of statin and NF-κB inhibitor (CAPE) resulted in decreased cell viability, Lin28B and cyclin D1 expression, synergistically. Of note, let-7 miRNA levels were restored after simvastatin treatment, and further increased their expression levels by CAPE double treatment. In order to confirm this mechanistic clue, we specifically inhibited Lin28B and NF-κB genes, respectively, resulting in increased cell apoptosis signaling in the Lin28b or NF-κB knock down cells by combined treatment with simvastatin. Conclusions: In conclusion, simvastatin inhibited the cell growth of various human CRPC cell lines by controlling NFkB-LIN28B-let7 miRNA signaling pathway, and therefore; concurrent NF-κB inhibition with simvastatin treatment induce the synergistic anti-cancer effects in human CRPC cells.

scholarly journals ISL1 Romotes Enzalutamide Resistance in Castration-resistant Prostate Cancer (CRPC) through Epithelial to Mesenchymal Transition (EMT)

2021 ◽  
Author(s):  
Jae Duck Choi ◽  
Tae Jin Kim ◽  
Byong Chang Jeong ◽  
Hwang Gyun Jeon ◽  
Seong Soo Jeon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Xenograft Model ◽  
Resistant Cell Line ◽  
Castration Resistant Prostate Cancer ◽  
Mesenchymal Transition ◽  
Knock Down ◽  
Castration Resistant

Abstract Abnormal expression of insulin gene enhancer-binding protein 1 (ISL1) has been demonstrated to be closely associated with cancer development and progression in several cancers. However, little is known about ISL1 expression in metastatic castration-resistant prostate cancer (CRPC). ISL1 has also been recognized as a positive modulator of epithelial-mesenchymal transition (EMT). In this study, we focused on ISL1 which showed maximum upregulation at the mRNA level in the enzalutamide-resistant cell line. Accordingly, we found that ISL1 was overexpressed in enzalutamide-resistant C4-2B cells and its expression was significantly related to EMT. Our findings reveal the important role of ISL1 in androgen receptor (AR)-dependent prostate cancer cell growth; ISL1 knockdown reduced the AR activity and cell growth. ISL1 knockdown using small-interfering RNA inhibited AR, PSA, and EMT-related protein expression in C4-2B ENZR cells. In addition, knock-down ISL1 reduced the levels of AKT and p65 phosphorylation in C4-2B ENZR cells and these suggest that knock-down ISL1 suppresses EMT in part by targeting the AKT/ NF-κB pathway. Further, ISL1 downregulation could effectively inhibit tumor growth in a human CRPC xenograft model. Together, the present study shows that downregulation of ISL1 expression is necessary for overcoming enzalutamide resistance and improving the survival of CRPC patients.

scholarly journals Human heterochromatin protein 1 isoforms regulate androgen receptor signaling in prostate cancer

2013 ◽  
Vol 50 (3) ◽  
pp. 401-409 ◽  
Author(s):  
Momoe Itsumi ◽  
Masaki Shiota ◽  
Akira Yokomizo ◽  
Eiji Kashiwagi ◽  
Ario Takeuchi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Androgen Receptor ◽  
Cell Growth ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Castration Resistant ◽  
22Rv1 Cell

Androgen receptor (AR) signaling is critical for the tumorigenesis and development of prostate cancer, as well as the progression to castration-resistant prostate cancer. We previously showed that the heterochromatin protein 1 (HP1) β isoform plays a critical role in transactivation of AR signaling as an AR coactivator that promotes prostate cancer cell proliferation. However, the roles of other HP1 isoforms, HP1α and HP1γ, in AR expression and prostate cancer remain unclear. Here, we found that knockdown of HP1γ, but not HP1α, reduced AR expression and cell proliferation by inducing cell cycle arrest at G1 phase in LNCaP cells. Conversely, overexpression of full-length HP1α and its C-terminal deletion mutant increased AR expression and cell growth, whereas overexpression of HP1γ had no effect. Similarly, HP1α overexpression promoted 22Rv1 cell growth, whereas HP1γ knockdown reduced the proliferation of CxR cells, a castration-resistant LNCaP derivative. Taken together, HP1 isoforms distinctly augment AR signaling and cell growth in prostate cancer. Therefore, silencing of HP1β and HP1γ may be a promising therapeutic strategy for treatment of prostate cancer.

scholarly journals Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Interacts with the Androgen Receptor (AR) and Promotes Prostate Cancer Cell Growth by Activating the AR

2010 ◽  
Vol 24 (1) ◽  
pp. 114-127 ◽  
Author(s):  
Masaki Shiota ◽  
Akira Yokomizo ◽  
Yasuhiro Tada ◽  
Junichi Inokuchi ◽  
Katsunori Tatsugami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Growth ◽  
Target Genes ◽  
Specific Antigen ◽  
Peroxisome Proliferator ◽  
Castration Resistant Prostate Cancer ◽  
Promoter Regions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Castration Resistant

Abstract There are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) was found to be an AR cofactor. PGC-1α interacted with the N-terminal domain of AR, was involved in the N- and C-terminal interaction of AR, and enhanced the DNA-binding ability of AR to androgen-responsive elements in the prostate-specific antigen enhancer and promoter regions to increase the transcription of AR target genes. Silencing of PGC-1α suppressed cell growth of AR-expressing prostate cancer (PCa) cells by inducing cell-cycle arrest at the G1 phase, similar to inhibition of androgen/AR signaling. Furthermore, PGC-1α knock-down also suppressed cell growth in the castration-resistant LNCaP-derivatives. These findings indicate that PGC-1α is involved in the proliferation of AR-expressing PCa cells by acting as an AR coactivator. Modulation of PGC-1α expression or function may offer a useful strategy for developing novel therapeutics for PCa, including CRPC, which depends on AR signaling by overexpressing AR and its coactivators.

scholarly journals ISL1 promotes enzalutamide resistance in castration-resistant prostate cancer (CRPC) through epithelial to mesenchymal transition (EMT)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae Duck Choi ◽  
Tae Jin Kim ◽  
Byong Chang Jeong ◽  
Hwang Gyun Jeon ◽  
Seong Soo Jeon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Xenograft Model ◽  
Resistant Cell Line ◽  
Castration Resistant Prostate Cancer ◽  
Mesenchymal Transition ◽  
Knock Down ◽  
Castration Resistant

AbstractAbnormal expression of insulin gene enhancer-binding protein 1 (ISL1) has been demonstrated to be closely associated with cancer development and progression in several cancers. However, little is known about ISL1 expression in metastatic castration-resistant prostate cancer (CRPC). ISL1 has also been recognized as a positive modulator of epithelial–mesenchymal transition (EMT). In this study, we focused on ISL1 which showed maximum upregulation at the mRNA level in the enzalutamide-resistant cell line. Accordingly, we found that ISL1 was overexpressed in enzalutamide-resistant C4-2B cells and its expression was significantly related to EMT. Our findings reveal the important role of ISL1 in androgen receptor (AR)-dependent prostate cancer cell growth; ISL1 knockdown reduced the AR activity and cell growth. ISL1 knockdown using small-interfering RNA inhibited AR, PSA, and EMT-related protein expression in C4-2B ENZR cells. In addition, knock-down ISL1 reduced the levels of AKT and p65 phosphorylation in C4-2B ENZR cells and these suggest that knock-down ISL1 suppresses EMT in part by targeting the AKT/NF-κB pathway. Further, ISL1 downregulation could effectively inhibit tumor growth in a human CRPC xenograft model. Together, the present study shows that downregulation of ISL1 expression is necessary for overcoming enzalutamide resistance and improving the survival of CRPC patients.

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