Role of RbBP5 and H3K4me3 in the vicinity of Snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell

30 Background: The hypoxia-inducible factor (HIF) transcription factor has already cemented its oncogenic role in the development of renal cell carcinoma (RCC). However, its role in the tumorigenesis of other solid tumors remains unspecificed. Our studies focus on a novel link between HIF and prostate carcinogenesis. Methods: Using both in vitro cell culture studies as well as in vivo studies (orthotopic xenograft and genetically engineered mouse models) we investigate the role of HIF in prostate cancer cell proliferation, invasion, and progression. Results: Both HIF1 and HIF2 appear to be necessary for the proliferation and invasion of prostate cancer cell lines in vitro. Preliminary analysis of a PTEN deficient mouse model of prostate cancer suggests that expression of a stabilized form of HIF2 promotes the development of a larger prostate tumor burden and a more aggressive histology (high grade prostate intraepithelial neoplasia [PIN] at earlier stages). Moreover, PTEN-deficient prostate tumors producing HIF2 are more proliferative and vascular and express increased levels of genes associated with epithelial to mesenchymal transition (EMT). Conclusions: There has been much interest in the role of angiogenesis and hypoxia in prostate cancer progression. Our preliminary data suggest that HIF2 is able to promote PTEN-deficient prostate cancer progression in mice by increasing proliferation, angiogenesis, and EMT. No significant financial relationships to disclose.

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MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in Prostate Cancer via Targeting RKIP

Cellular Physiology and Biochemistry ◽

10.1159/000464120 ◽

2017 ◽

Vol 41 (3) ◽

pp. 1135-1146 ◽

Cited By ~ 36

Author(s):

Yang Du ◽

Xiu-heng Liu ◽

Heng-cheng Zhu ◽

Lei Wang ◽

Jin-zhuo Ning ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

In Vivo Studies ◽

Mesenchymal Transition ◽

Proliferation And Metastasis

Background/Aims: MicroRNAs (miRNAs, miRs) have emerged as important post-transcriptional regulators in various cancers. miR-543 has been reported to play critical roles in hepatocellular carcinoma and colorectal cancer, however, the role of miR-543 in the pathogenesis of prostate cancer has not been fully understood. Methods: Expression of miR-543 and Raf Kinase Inhibitory Protein (RKIP) in clinical prostate cancer specimens, two prostate cancer cell lines, namely LNCAP and C4-2B, were determined. The effects of miR-543 on proliferation and metastasis of tumor cells were also investigated with both in vitro and in vivo studies. Results: miR-543 was found to be negatively correlated with RKIP expression in clinical tumor samples and was significantly upregulated in metastatic prostate cancer cell line C4-2B compared with parental LNCAP cells. Further studies identified RKIP as a direct target of miR-543. Overexpression of miR-543 downregulated RKIP expression and promoted the proliferation and metastasis of cancer cells, whereas knockdown of miR-543 increased expression of RKIP and suppressed the proliferation and metastasis of cancer cells in vitro and in vivo. Conclusion: Our study demonstrates that miR-543 promotes the proliferation and metastasis of prostate cancer via targeting RKIP.

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