Abstract
BackgroundRecent reports have suggested a possible involvement of Single-minded homolog 2 (SIM2) in human solid cancers, including prostate cancer. However, the exact role of SIM2 in cancer in general, and in prostate cancer in particular, remains largely unknown. This study was designed to elucidate the role of SIM2 in prostate cancer using a shRNA-based approach in the PC3 prostate cancer cell line.MethodsLentiviral shRNAs were used to inhibit SIM2 gene and protein levels in PC3 cells. Quantitative RT-PCR and branched DNA were performed to evaluate transcript expression. SIM2 protein expression level was measured by western blot. Profiling of gene expression spanning the whole genome, as well as polar metabolomics of several major metabolic pathways was performed to identify major pathway dysregulations.ResultsSIM2 gene and protein products were significantly downregulated by lenti-shRNA in PC3 cell line. This low expression of SIM2 affected gene expression profile, revealing significant changes in major signaling pathways, networks and functions. In addition, major metabolic pathways were affected.ConclusionTaken together, our results suggest an involvement of SIM2 in key traits of prostate tumor cell biology and might underlie a contribution of this transcription factor to prostate cancer onset and progression.
Highlights
Single-minded homolog 2 (SIM2) gene is located on the human chromosome 21q22.2 and is a member of the basic helix-loop-helix PAS [per-Arnt-Sim] family of transcription factors [1,2]
We have evaluated SIM2 gene expression in a total of 24 normal and tumor prostatectomy samples shown in table 1
Because SIM2 gene exists in two isoforms, SIM2 short (SIM2s) and SIM2 long (SIM2L), we confirmed the expression of both isoforms in RNA extracted from prostatectomy using branched DNA technique (Fig. 1A & 1B)
Summary
Single-minded homolog 2 (SIM2) gene is located on the human chromosome 21q22.2 and is a member of the basic helix-loop-helix PAS [per-Arnt-Sim] (bHLH-PAS) family of transcription factors [1,2]. As a transcription factor (TF), murine SIM2 (mSIM2) mediates gene expression through CNS midline enhancer (CME) element with its dimerization partner ARNT via ARNT carboxy-terminus [4]. Antisense inhibition of SIM2-s expression by antisense oligos caused growth inhibition and apoptosis in colon cancer cell line RKO and tumor growth in nude mice and in pancreatic cancer cell line CAPAN-. Recent reports have suggested a possible involvement of Single-minded homolog 2 (SIM2) in human solid cancers, including prostate cancer. This study was designed to elucidate the role of SIM2 in prostate cancer using a shRNA-based approach in the PC3 prostate cancer cell line
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have