Project description:The study was aimed at identifying genes directly or indirectly regulated by miR-205 in the prostate. To this purpose, DU145 prostate cancer cells, which express miR-205 at very low levels, were transfected with miR-205 synthetic precursor and consequent alterations of gene expression analyzed using a microarray approach. Keywords: comparison betweed cells exposed to different miRNA precursors
Project description:To identify differentially expressed genes by anti cancer treatments (microRNAs or siRNAs) in human cancer, several cell lines (bladder cancer, prostate cancer, renal cell carcinoma, oral squamous cell carcinoma and lung squamous cell carcinoma) were subjected to Agilent whole genome microarrays. Human cancer cell lines (SAS, HSC3, BOY, T24, PC3, PC3M, DU145, C4-2, 786-O, A-498 and EBC-1) were treated with miRNAs (miR-205, miR-29a, miR-144-3p, miR-144-5p, miR-451, miR-210, miR-145-5p, miR-145-3p, miR-23b cluster, miR-221, miR-222 and miR-223), siRNAs (si-GOLM1, si-HMGB3, si-CENPF, si-LOXL2, si-TMEM184B and si-CORO1C).
Project description:In this study, the prognostic properties of miR-205 expression levels are investigated in a well-documented prostate cancer cohort. We show that miR-205 is correlated to shortened overall survival, significantly dividing the PCa patients into high and low risk groups. Furthermore, miR-205 is shown to inversely correlate to occurrence of metastases. In situ hybridization is also performed, demonstrating high miR-205 expression in the basal cells of benign prostate tissue glands. A RIP-Chip assay using an AGO2 antibody was implemented and the miR-205 targets identified were found to be enriched in MAPK/ERK, Toll-like receptor and IL-6 signaling pathways. We also found individual targets involved in cancer and androgen receptor signaling. Ectopic levels of miR-205 are shown to decrease the level of androgen receptor both at the mRNA and protein levels in prostate cancer cell lines. This is further corroborated in the prostate cancer cohort were miR-205 expression levels in the prostatic tissues are found to inversely correlate to assessment of androgen receptor (AR) immunostaining and to serum levels of PSA, a protein regulated by AR signaling. The level of miR-205 is also found to be significantly lower in castration resistant prostate cancer patients than in hormone naïve patients. Our data indicates that miR-205 is regulated by androgens and act by different mechanisms in androgen depleted settings, e.g. giving opposite effects on adhesion. Taken together these findings imply that miR-205 might have therapeutic potential especially for the castration resistant and currently untreatable form of prostate cancer.
Project description:In this study, the prognostic properties of miR-205 expression levels are investigated in a well-documented prostate cancer cohort. We show that miR-205 is correlated to shortened overall survival, significantly dividing the PCa patients into high and low risk groups. Furthermore, miR-205 is shown to inversely correlate to occurrence of metastases. In situ hybridization is also performed, demonstrating high miR-205 expression in the basal cells of benign prostate tissue glands. A RIP-Chip assay using an AGO2 antibody was implemented and the miR-205 targets identified were found to be enriched in MAPK/ERK, Toll-like receptor and IL-6 signaling pathways. We also found individual targets involved in cancer and androgen receptor signaling. Ectopic levels of miR-205 are shown to decrease the level of androgen receptor both at the mRNA and protein levels in prostate cancer cell lines. This is further corroborated in the prostate cancer cohort were miR-205 expression levels in the prostatic tissues are found to inversely correlate to assessment of androgen receptor (AR) immunostaining and to serum levels of PSA, a protein regulated by AR signaling. The level of miR-205 is also found to be significantly lower in castration resistant prostate cancer patients than in hormone naïve patients. Our data indicates that miR-205 is regulated by androgens and act by different mechanisms in androgen depleted settings, e.g. giving opposite effects on adhesion. Taken together these findings imply that miR-205 might have therapeutic potential especially for the castration resistant and currently untreatable form of prostate cancer. Experiment done with biological triplicates. Three with miR-205 ectopic expression and three with negative control mimic ectopic expression. Followed by a RIP-Chip, ending with mRNA extraction and gene expression array.
Project description:Recent studies demonstrate both basal and luminal cells of the prostate gland can initiate tumorigenesis upon oncogenic transformation. However, it remains unclear how molecular mechanisms operating within each cell lineage contribute to the initiation and progression of the prostate cancer. Here we investigate functions of individual miRNAs using genetically engineered mouse models. By both quantitative miR-Seq and in situ hybridization, we identify microRNA-205 (miR-205) as the most highly expressed miRNA and specific to the basal cells in the prostate. MicroRNA-205 expression is further elevated in the basal cells in the well-established Pten null tumorigenic mouse model. To investigate the role of miR-205 in Pten-deletion mediated tumorigenesis, we generated a Pten/miR-205 double knockout mouse model. Concurrent deletion of both miR-205 and Pten significantly compromised tumor progression in both basal and luminal compartments. We observed significantly reduced tumor size and compromised proliferation in both basal and luminal cells. We have previously demonstrated a critical requirement of miR-205 for maintaining the PI(3)K signaling and pAkt levels in skin stem cells. Consistent with this role, we observed strong reduction of pAkt and significantly increased cellular senescence in the basal cells of the dKO, compared to the Pten KO alone. These results suggest that miR-205 is cell-autonomously required for the tumorigenesis of the basal cells. Taken together, we have identified miR-205 as an important regulator in prostate cancer. Our study also reveals an essential and unexpected role of the basal cells for promoting prostate tumorigenesis.
Project description:This SuperSeries is composed of the following subset Series: GSE17315: mRNA expression upon reconstitution of miR-130a, miR-203 and miR-205 in prostate cancer cell line LNCaP GSE17317: miRNA expression in LNCaP, PC3, Du-145 and RWPE-1 cell lines GSE22979: Profiling of direct mRNA targets of miR-130a, miR-203 and miR-205 in prostate cancer cell line LNCaP Refer to individual Series