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 language | English |
|---|---|
| Pages (from-to) | 140-152 |
| Number of pages | 13 |
| Journal | Molecular cancer research : MCR |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2020 |
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ASJC Scopus subject areas
- Molecular Biology
- Oncology
- Cancer Research
Cite this
RAIN Is a Novel Enhancer-Associated lncRNA That Controls RUNX2 Expression and Promotes Breast and Thyroid Cancer. / Rossi, Teresa; Pistoni, Mariaelena; Sancisi, Valentina; Gobbi, Giulia; Torricelli, Federica; Donati, Benedetta; Ribisi, Salvatore; Gugnoni, Mila; Ciarrocchi, Alessia.
In: Molecular cancer research : MCR, Vol. 18, No. 1, 01.01.2020, p. 140-152.Research output: Contribution to journal › Article
}
TY - JOUR
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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85077477564&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-19-0564
DO - 10.1158/1541-7786.MCR-19-0564
M3 - Article
C2 - 31624086
AN - SCOPUS:85077477564
VL - 18
SP - 140
EP - 152
JO - Molecular Cancer Research
JF - Molecular Cancer Research
SN - 1541-7786
IS - 1
ER -