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Series GSE68045 Query DataSets for GSE68045
Status Public on Jan 01, 2017
Title Nucleotide stress induction of HEXIM1 suppresses melanoma by modulating cancer cell-specific gene transcription [FAST-iCLIP]
Organism Homo sapiens
Experiment type Other
Summary Cancer metabolism has been actively studied to gain insights into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a novel melanoma suppressor that participates in nucleotide stress regulation. HEXIM1 expression is low in melanoma. Its overexpression suppresses melanoma while its inactivation accelerates tumor onset in vivo. HEXIM1 responds to nucleotide stress. Knockdown of HEXIM1 rescues neural crest and melanoma nucleotide stress phenotypes in vivo. Mechanistically, under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to pause transcription at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic transcripts to bind to and be stabilized by HEXIM1. HEXIM1 therefore plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals a novel role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma.
 
Overall design FAST-iCLIP analysis of HEXIM1 in human A375 melanoma cells treated with either DMSO or 25 μM A771726 for 48 hrs.
 
Contributor(s) Tan JL, Flynn RA, Yang S, Zhou Y, Chang HY, Zon LI
Citation(s) 27058786
Submission date Apr 20, 2015
Last update date May 15, 2019
Contact name Leonard Zon
E-mail(s) zon@enders.tch.harvard.edu
Organization name Boston Children's Hospital
Department Oncology/Hematology
Street address 1 Blackfan Circle
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (4)
GSM1661548 HEXIM1+DMSO iCLIP Biological Replicate 1
GSM1661549 HEXIM1+DMSO iCLIP Biological Replicate 2
GSM1661550 HEXIM1+A771726 iCLIP Biological Replicate 1
This SubSeries is part of SuperSeries:
GSE68053 Nucleotide stress induction of HEXIM1 suppresses melanoma by modulating cancer cell-specific gene transcription
Relations
BioProject PRJNA281629
SRA SRP057454

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE68045_A375_HEXIM_A771726_T3_norm.bw 212.6 Kb (ftp)(http) BW
GSE68045_A375_HEXIM_DMSO_T3_norm.bw 172.6 Kb (ftp)(http) BW
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Raw data are available in SRA
Processed data are available on Series record

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