Potential prognostic value of miR-132 and miR-212 expression in mCRPC patients

To the Editor, we have been very pleased to read the interesting work proposed by Salemi et al. regarding the expression of specific fragments of microRNA (miRNA), particularly miR-132 and miR-212, as potential key regulators in prostate cancer (PCa). As outlined by the Authors, the altered expression of miRNAs in cancer pathogenesis represents a well-consolidated knowledge in the current literature. More specifically, both miR-212 and miR-132 regulate subsets of genes involved in tumor progression in several tumor cell types as PCa, proving a central role in tumorigenesis, cell adhesion, and angiogenesis. In addition, a strong association between miR-132 expression and high Gleason score PCa has been lately depicted [...].

VPRBP functions downstream of the androgen receptor and OGT to restrict p53 activation in prostate cancer

Androgen receptor (AR) is a major driver of prostate cancer (PCa) initiation and progression. O-GlcNAc transferase (OGT), the enzyme that catalyses the covalent addition of UDP-N-acetylglucosamine (UDP-GlcNAc) to serine and threonine residues of proteins, is often up-regulated in PCa with its expression correlated with high Gleason score. In this study we have identified an AR and OGT co-regulated factor, VPRBP/DCAF1. We show that VPRBP is regulated by the AR at the transcript level, and by OGT at the protein level. In human tissue samples, VPRBP protein expression correlated with AR amplification, OGT overexpression and poor prognosis. VPRBP knockdown in prostate cancer cells led to a significant decrease in cell proliferation, p53 stabilization, nucleolar fragmentation and increased p53 recruitment to the chromatin. In conclusion, we have shown that VPRBP/DCAF1 promotes prostate cancer cell proliferation by restraining p53 activation under the influence of the AR and OGT.

Relationship Between Vascular Endothelial Growth Factor Expression and Gleason Score in Prostate Carcinoma

A B S T R A C TBackground Prostate cancer is the most common cancer in men worldwide and rankssecond in the Laboratory of Anatomical Pathology, Dr. Mohammad Hoesin with thehighest incidence, especially at the age of more than 60 years. Factors that play a roleas a prognostic factor and therapy in prostate carcinoma, including VEGF. The roleof VEGF expression in prostate carcinoma as a prognostic and histopathological factorwhich is an important predictor for the progression of prostate carcinoma. This studyaims to determine the relationship between VEGF expression and Gleason score inprostate carcinoma. Method This study was a cross-sectional observational study.Thirty samples diagnosed with prostate adenocarcinoma were derived from the resultsof the tranurethral resection of the prostate (TRUP) and prostatectomy. Samples weretaken from the archives in the Anatomic Pathology section of Dr. Mohammad HoesinPalembang (period January 1, 2011 to December 31, 2013. Then the sample wasstained with VEGF antibody, identified and analyzed the VEGF relationship with theGleason.z score. Results The positivity of VEGF expression in prostateadenocarcinoma tended to be more prevalent in the Gleason score group ≥ 7 (43.3%)than in the Gleason score group <(10%). There was no significant relationship betweenVEGF expression and high Gleason score (p> 0.05). Conclusion There was nosignificant relationship between VEGF expression and Gleason score in prostateadenocarcinoma

miR-138-5p inhibits the malignant progression of prostate cancer by targeting FOXC1

Background: This study aimed to uncover the effect of miR-138-5p on the proliferation and metastasis of PCa cell lines, and further explore the potential regulatory mechanisms via regulating FOXC1.Methods: 60 pairs cancer tissues and corresponding paracancerous ones from PCa patients were collected to assess the expression level of miR-138-5p by qRT-PCR. Subsequently, over-expression of miR-138-5p were established to explore the proliferation and metastasis of miR-138-5p in PCa cell lines was analyzed by CCK-8, Tranwell assay and Wounding healing assay, respectively. Bioinformatics analysis and luciferase reporter gene assay were performed to search for the target genes of miR-138-5p, and FOXC1 was selected. Finally, the biological role of miR-138-5p and FOXC1 in the progression of PCa was clarified by a series of rescue experiments. Results: The results of qRT-PCR revealed that miR-138-5p was lowly expressed in PCa tissues and cell lines. Besdies, the PCa patients with low-miR-138-5p had a high Gleason score, lymph node metastasis and poor prognosis of PCa, compared with these patients with high-miR-138-5p. Over-expression of miR-138-5p inhibited the proliferative, migratory and invasive capacities of PC-3 and DU-145 cells. Bioinformatics analysis and luciferase reporter gene assay suggested that FOXC1 was predicted to be the target gene of miR-138-5p. Moreover, FOXC1 expression level was negatively correlated to that of miR-138-5p in PCa tissues. Importantly, Over-expression of FOXC1 could reverse miR-138-5p mimic induced-inhibition of PCa malignant progression.Conclusions: Downregulated miR-138-5p was closely associated with high Gleason score, more lymph node metastasis and poor prognosis of PCa patients. In addition, miR-138-5p alleviated the malignant progression of PCa by targeting and downregulating FOXC1.

Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer

The androgen receptor (AR) plays a critical role in the development and the progression of prostate cancer. Alterations in theexpression of AR coregulators lead to AR hypersensitivity, which is one of the mechanisms underlying the progression ofprostate cancer into a castrate-resistant state. Octamer transcription factor 1 (Oct1) is a ubiquitous member of the POUhomeodomainfamily that functions as a coregulator of AR. In our study, the contribution of Oct1 to prostate cancerdevelopment was examined. Immunocytochemistry analysis showed that Oct1 is expressed in the nuclei of LNCaP cells.siRNA-mediated silencing of Oct1 expression inhibited LNCaP cell proliferation. Immunohistochemical analysis of Oct1expression in tumor specimens obtained from 102 patients with prostate cancer showed a positive correlation of Oct1immunoreactivity with a high Gleason score and AR immunoreactivity (p 5 0.0042 and p &lt; 0.0001, respectively). Moreover,patients with high immunoreactivity of Oct1 showed a low cancer-specific survival rate, and those patients with highimmunoreactivities of both Oct1 and AR exhibited poorer cancer-specific prognosis. Multivariate hazard analysis revealed asignificant correlation between high Oct1 immunoreactivity and poor cancer-specific survival (p 5 0.012). These resultsdemonstrate that Oct1 can be a prognostic factor in prostate cancer as a coregulator of AR and may lead to the developmentof a new therapeutic intervention for prostate cancer.