MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity.

Oncogene
Nichelle C. WhitlockAdam G. Sowalsky

Abstract

Localized prostate cancer develops very slowly in most men, with the androgen receptor (AR) and MYC transcription factors amongst the most well-characterized drivers of prostate tumorigenesis. Canonically, MYC up-regulation in luminal prostate cancer cells functions to oppose the terminally differentiating effects of AR. However, the effects of MYC up-regulation are pleiotropic and inconsistent with a poorly proliferative phenotype. Here we show that increased MYC expression and activity are associated with the down-regulation of MEIS1, a HOX-family transcription factor. Using RNA-seq to profile a series of human prostate cancer specimens laser capture microdissected on the basis of MYC immunohistochemistry, MYC activity, and MEIS1 expression were inversely correlated. Knockdown of MYC expression in prostate cancer cells increased the expression of MEIS1 and increased the occupancy of MYC at the MEIS1 locus. Finally, we show in laser capture microdissected human prostate cancer samples and the prostate TCGA cohort that MEIS1 expression is inversely proportional to AR activity as well as HOXB13, a known interacting protein of both AR and MEIS1. Collectively, our data demonstrate that elevated MYC in a subset of primary prostate ...Continue Reading

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Citations

Dec 10, 2020·American Journal of Physiology. Cell Physiology·Mingzhu JiangAihua Zhang
Jan 1, 2021·Non-coding RNA·Kasper Thystrup KarstensenSakari Kauppinen

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Methods Mentioned

BETA
biopsies
laser capture microdissection
RNA-seq
ChIP-seq
ChIP
reverse-transcription PCR
immunoprecipitation
biopsy

Software Mentioned

ssGSEA
ssGSEA Projection
HOMER
GSEA
Definiens Tissue Studio
GraphPad Prism

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