Genomics

Dataset Information

41

Nucleotide stress induction of HEXIM1 suppresses melanoma by modulating cancer cell-specific gene transcription [FAST-iCLIP]


ABSTRACT: 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.

INSTRUMENT(S): Illumina NextSeq 500 (Homo sapiens)

SUBMITTER: Leonard Zon  

PROVIDER: GSE68045 | GEO | 2017-01-01

SECONDARY ACCESSION(S): PRJNA281629

REPOSITORIES: GEO

Dataset's files

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GSE68045_A375_HEXIM_A771726_T3_norm.bw Other
GSE68045_A375_HEXIM_DMSO_T3_norm.bw Other
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Publications


Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferatio  ...[more]

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