Consulting prostate cancer cohort data uncovers transcriptional control: Regulation of the MARCH6 gene

Publication date: Available online 15 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Hudson W. Coates, Ngee Kiat Chua, Andrew J. BrownAbstractCholesterol accumulation is a hallmark of prostate cancer (PCa) enabled by upregulation of its synthesis, which presents a potential therapeutic target. This pathway is suppressed by the E3 ubiquitin ligase membrane-associated RING-CH-type finger 6 (MARCH6); however, little is known of MARCH6 regulation, particularly at the transcriptional level. Here, we consulted large transcriptomic PCa datasets to investigate transcription factors and DNA sequence elements that regulate the MARCH6 gene. Amongst 498 primary PCa tissues of The Cancer Genome Atlas, we identified a striking positive correlation between MARCH6 and androgen receptor (AR) gene expression (r = 0.81, p < 1 × 10−117) that held in other primary tumour datasets. Two putative androgen response elements were identified in the MARCH6 gene using motif prediction and mining of publicly accessible chromatin immunoprecipitation-sequencing data. However, MARCH6 expression was not androgen-responsive in luciferase reporter and qRT-PCR assays. Instead, we established that the MARCH6–AR correlation in primary PCa is due to common regulation by the transcription factor Sp1. We located a region 100 bp downstream of the MARCH6 transcriptional start site that contains three Sp1 binding sites and strongly upregulat...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research