Project description:Metastatic prostate cancer (PCa) is a terminal disease and establishment of novel therapeutic strategy specifically targeting metastasis is critically required for its management. This study was aimed at identifying metastasis-driving genes which could potentially be therapeutic targets for metastatic prostate cancer. Integrative analysis of gene expression profiles from a pair of metastatic and non-metastatic prostate cancer tissue xenografts was used to identify potential prostate cancer metastasis-driving genes. Among the candidate genes found, GATA2, a master regulator gene in the development of hematopoietic system, was particularly interesting since it is an important pioneer factor in the regulation of AR-target gene in prostate cancer. In consistent with our finding, elevated expression of the GATA2 gene in metastatic prostate cancers was found and its expression was significantly correlated with poor prognosis in prostate cancer patients. Furthermore, indication of the GATA2 gene maybe the metastasis-driving gene was evidenced in decreased of cell migration, tissue invasion and focal adhesion disassembly in GATA2-down-regulated LNCaP cells. Global gene expression analysis after silencing of the GATA2 gene revealed a significant changed in cell transcriptomes with ~ 2500 genes with > 2 fold mRNA level changed and FDR <0.05, indicates that GATA2 plays a critical role in cell reprogramming as pioneer factor in the development of prostate cancer metastasis. LNCaP human prostate cancer cells transiently knockdown with siRNA that specifically targeting GATA2 (siGATA2) or scrambled siRNA (sicontrol). RNAs were isolated from cells after 72 hours of incubation. Gene expression profiles of four biological replicates from each sample group were analyzed to identify differentially regulated downstream genes after knockdown of GATA2.
Project description:SChLAP1 is a novel long non-coding RNA expressed in prostate cancer. Here we performed transcriptional profiling of the prostate cancer cell lines LNCaP and 22Rv1 comparing non-targeting siRNA treatment versus SChLAP1-siRNA treatment. Goal was to determine the effect of SChLAP1 knockdown on gene expression in prostate cancer. Two-condition experiment: non-targeting siRNA versus SChLAP1 siRNA treated cells. Biological replicates: 1 control replicate, 2 treatment replicates. Technical replicates: 3 replicates per SChLAP1 siRNA. Cell lines: 22Rv1 and LNCaP.
Project description:SChLAP1 is a novel long non-coding RNA expressed in prostate cancer. Here we performed transcriptional profiling of the prostate cancer cell lines LNCaP and 22Rv1 comparing non-targeting siRNA treatment versus SChLAP1-siRNA treatment. Goal was to determine the effect of SChLAP1 knockdown on gene expression in prostate cancer.
Project description:We investigated the role of GATA2 in prostate cancer cells beyond the AR signaling axis, and characterized the pharmacological potency of the GATA2 small molecule inhibitor (SMI) K-11706 against prostate cancer cells. K-11706, which inhibited the proliferation and invasive behavior of PC cells, and dramatically reduced the genome-wide transcriptional activity of GATA2, AR, and cMyc, leading to downregulation of several prostate cancer drivers and AR/cMyc effector genes, notably FOXM1, EZH2, and CENPF. Transcriptional profiling and functional pathway analysis of the K-11706 transcriptomic footprint against curated databases delineated a biological network composed of genes involved in cell cycle/proliferation, stemness, metastasis and DNA repair.