RAIN Is a Novel Enhancer-Associated lncRNA That Controls RUNX2 Expression and Promotes Breast and Thyroid Cancer

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Abstract

Enhancer (ENH)-associated long noncoding RNAs (lncRNA) are a peculiar class of RNAs produced by transcriptionally active ENHs, owning potential gene-regulatory function. Here, we characterized RAIN, a novel ENH-associated lncRNA. Analysis of RAIN expression in a retrospective cohort of human thyroid cancers showed that the expression of this lncRNA is restricted to cancer cells and strongly correlates with the expression of the cancer-promoting transcription factor RUNX2. We showed that RAIN, serving as a cis-regulatory element, promotes RUNX2 expression by two mechanisms. Binding WDR5 and facilitating its localization on the RUNX2 promoter, RAIN modifies the transcriptional status of the RUNX2 locus facilitating transcription initiation. In parallel, RAIN acts as decoy for negative elongation factor complex, restraining its inhibitory function on transcription elongation. In both thyroid and breast cancer cells, RAIN promotes oncogenic features. Using RNA-sequencing profiling, we showed that RAIN orchestrates the expression of a network of cancer-promoting transcription regulators, suggesting that RAIN affects cancer cell phenotype by coordinating the expression of a complex transcriptional network. IMPLICATIONS: Our data contribute to understand lncRNA function in gene regulation and to consolidate their role in cancer.

Original languageEnglish
Pages (from-to)140-152
Number of pages13
JournalMolecular cancer research : MCR
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

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Long Noncoding RNA
Thyroid Neoplasms
Breast Neoplasms
Neoplasms
RNA Sequence Analysis
Gene Regulatory Networks
Regulator Genes
Transcription Factors
RNA
Phenotype
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

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title = "RAIN Is a Novel Enhancer-Associated lncRNA That Controls RUNX2 Expression and Promotes Breast and Thyroid Cancer",
abstract = "Enhancer (ENH)-associated long noncoding RNAs (lncRNA) are a peculiar class of RNAs produced by transcriptionally active ENHs, owning potential gene-regulatory function. Here, we characterized RAIN, a novel ENH-associated lncRNA. Analysis of RAIN expression in a retrospective cohort of human thyroid cancers showed that the expression of this lncRNA is restricted to cancer cells and strongly correlates with the expression of the cancer-promoting transcription factor RUNX2. We showed that RAIN, serving as a cis-regulatory element, promotes RUNX2 expression by two mechanisms. Binding WDR5 and facilitating its localization on the RUNX2 promoter, RAIN modifies the transcriptional status of the RUNX2 locus facilitating transcription initiation. In parallel, RAIN acts as decoy for negative elongation factor complex, restraining its inhibitory function on transcription elongation. In both thyroid and breast cancer cells, RAIN promotes oncogenic features. Using RNA-sequencing profiling, we showed that RAIN orchestrates the expression of a network of cancer-promoting transcription regulators, suggesting that RAIN affects cancer cell phenotype by coordinating the expression of a complex transcriptional network. IMPLICATIONS: Our data contribute to understand lncRNA function in gene regulation and to consolidate their role in cancer.",
author = "Teresa Rossi and Mariaelena Pistoni and Valentina Sancisi and Giulia Gobbi and Federica Torricelli and Benedetta Donati and Salvatore Ribisi and Mila Gugnoni and Alessia Ciarrocchi",
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T1 - RAIN Is a Novel Enhancer-Associated lncRNA That Controls RUNX2 Expression and Promotes Breast and Thyroid Cancer

AU - Rossi, Teresa

AU - Pistoni, Mariaelena

AU - Sancisi, Valentina

AU - Gobbi, Giulia

AU - Torricelli, Federica

AU - Donati, Benedetta

AU - Ribisi, Salvatore

AU - Gugnoni, Mila

AU - Ciarrocchi, Alessia

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Enhancer (ENH)-associated long noncoding RNAs (lncRNA) are a peculiar class of RNAs produced by transcriptionally active ENHs, owning potential gene-regulatory function. Here, we characterized RAIN, a novel ENH-associated lncRNA. Analysis of RAIN expression in a retrospective cohort of human thyroid cancers showed that the expression of this lncRNA is restricted to cancer cells and strongly correlates with the expression of the cancer-promoting transcription factor RUNX2. We showed that RAIN, serving as a cis-regulatory element, promotes RUNX2 expression by two mechanisms. Binding WDR5 and facilitating its localization on the RUNX2 promoter, RAIN modifies the transcriptional status of the RUNX2 locus facilitating transcription initiation. In parallel, RAIN acts as decoy for negative elongation factor complex, restraining its inhibitory function on transcription elongation. In both thyroid and breast cancer cells, RAIN promotes oncogenic features. Using RNA-sequencing profiling, we showed that RAIN orchestrates the expression of a network of cancer-promoting transcription regulators, suggesting that RAIN affects cancer cell phenotype by coordinating the expression of a complex transcriptional network. IMPLICATIONS: Our data contribute to understand lncRNA function in gene regulation and to consolidate their role in cancer.

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