Oncotarget

Research Papers:

Comparative RNA-seq analysis reveals dys-regulation of major canonical pathways in ERG-inducible LNCaP cell progression model of prostate cancer

Parameet Kumar _, Joyeeta Chakraborty, Gauthaman Sukumar, Clifton Dalgard, Raghunath Chatterjee and Roopa Biswas _

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Oncotarget. 2019; 10:4290-4306. https://doi.org/10.18632/oncotarget.27019

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Abstract

Parameet Kumar1, Joyeeta Chakraborty2, Gauthaman Sukumar1,3, Clifton Dalgard1,4, Raghunath Chatterjee2 and Roopa Biswas1

1 Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

2 Human Genetics Unit, Indian Statistical Institute, Kolkata, India

3 Collaborative Health Initiative Research Program, Henry Jackson Foundation, Bethesda, MD, USA

4 The American Genome Center, Uniformed Service University of the Health Sciences, Bethesda, MD, USA

Correspondence to:

Roopa Biswas,email: roopa.biswas@usuhs.edu
Parameet Kumar,email: parameet.kumar.ctr@usuhs.edu

Keywords: RNAseq; prostate cancer; LNCaP cells; ERG; mRNA

Received: December 29, 2018     Accepted: May 30, 2019     Published: July 02, 2019

ABSTRACT

Prostate Cancer (CaP) is the second leading cause of cancer related death in USA. In human CaP, gene fusion between androgen responsive regulatory elements at the 5'-untranslated region of TMPRSS2 and ETS-related genes (ERG) is present in at least 50% of prostate tumors. Here we have investigated the unique cellular transcriptome associated with over-expression of ERG in ERG-inducible LNCaP cell model system of human CaP. Comprehensive transcriptome analyses reveal a distinct signature that distinguishes ERG dependent and independent CaP in LNCaP cells. Our data highlight a significant heterogeneity among the transcripts. Out of the 526 statistically significant differentially expressed genes, 232 genes are up-regulated and 294 genes are down-regulated in response to ERG. These ERG-associated genes are linked to several major cellular pathways, cell cycle regulation being the most significant. Consistently our data indicate that ERG plays a key role in modulating the expression of genes required for G1 to S phase transition, particularly those that affect cell cycle arrest at G1 phase. Moreover, cell cycle arrest in response to ERG appears to be promoted by induction of p21 in a p53 independent manner. These findings may provide new insights into mechanisms that promote growth and progression of CaP.


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