Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis

Rebekah Brooks; Judith Monzy; Bailey Aaron; Xue Zhang; Andrew Kossenkov; James Hayden; Frederick Keeney; David W. Speicher; Lin Zhang; Chi V. Dang

doi:10.1016/j.celrep.2022.111514

Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis

Rebekah Brooks, Judith Monzy, Bailey Aaron, Xue Zhang, Andrew Kossenkov, James Hayden, Frederick Keeney, David W. Speicher, Lin Zhang, Chi V. Dang

Research output: Contribution to journal › Article › peer-review

Abstract

We identify ADIRF-AS1 circadian long non-coding RNA (lncRNA). Deletion of ADIRF-AS1 in U2OS cells alters rhythmicity of clock-controlled genes and expression of extracellular matrix genes. ADIRF-AS1 interacts with all components of the PBAF (PBRM1/BRG1) complex in U2OS cells. Because PBRM1 is a tumor suppressor mutated in over 40% of clear cell renal carcinoma (ccRCC) cases, we evaluate ADIRF-AS1 in ccRCC cells. Reducing ADIRF-AS1 expression in ccRCC cells decreases expression of some PBAF-suppressed genes. Expression of these genes is partially rescued by PBRM1 loss, consistent with ADIRF-AS1 acting in part to modulate PBAF. ADIRF-AS1 expression correlates with survival in human ccRCC, particularly in PBRM1 wild-type, but not mutant, tumors. Loss of ADIRF-AS1 eliminates in vivo tumorigenesis, partially rescued by concurrent loss of PBRM1 only when co-injected with Matrigel, suggesting a PBRM1-independent function of ADIRF-AS1. Our findings suggest that ADIRF-AS1 functions partly through PBAF to regulate specific genes as a BMAL1-CLOCK-regulated, oncogenic lncRNA.

Original language	English (US)
Article number	111514
Journal	Cell Reports
Volume	41
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2022.111514
State	Published - Oct 18 2022
Externally published	Yes

Keywords

ADIRF-AS1
CP: Cancer
PBAF
ccRCC
circadian rhythm
clock
lncRNA

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2022.111514

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title = "Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis",

abstract = "We identify ADIRF-AS1 circadian long non-coding RNA (lncRNA). Deletion of ADIRF-AS1 in U2OS cells alters rhythmicity of clock-controlled genes and expression of extracellular matrix genes. ADIRF-AS1 interacts with all components of the PBAF (PBRM1/BRG1) complex in U2OS cells. Because PBRM1 is a tumor suppressor mutated in over 40% of clear cell renal carcinoma (ccRCC) cases, we evaluate ADIRF-AS1 in ccRCC cells. Reducing ADIRF-AS1 expression in ccRCC cells decreases expression of some PBAF-suppressed genes. Expression of these genes is partially rescued by PBRM1 loss, consistent with ADIRF-AS1 acting in part to modulate PBAF. ADIRF-AS1 expression correlates with survival in human ccRCC, particularly in PBRM1 wild-type, but not mutant, tumors. Loss of ADIRF-AS1 eliminates in vivo tumorigenesis, partially rescued by concurrent loss of PBRM1 only when co-injected with Matrigel, suggesting a PBRM1-independent function of ADIRF-AS1. Our findings suggest that ADIRF-AS1 functions partly through PBAF to regulate specific genes as a BMAL1-CLOCK-regulated, oncogenic lncRNA.",

keywords = "ADIRF-AS1, CP: Cancer, PBAF, ccRCC, circadian rhythm, clock, lncRNA",

author = "Rebekah Brooks and Judith Monzy and Bailey Aaron and Xue Zhang and Andrew Kossenkov and James Hayden and Frederick Keeney and Speicher, {David W.} and Lin Zhang and Dang, {Chi V.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

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doi = "10.1016/j.celrep.2022.111514",

language = "English (US)",

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T1 - Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis

AU - Brooks, Rebekah

AU - Monzy, Judith

AU - Aaron, Bailey

AU - Zhang, Xue

AU - Kossenkov, Andrew

AU - Hayden, James

AU - Keeney, Frederick

AU - Speicher, David W.

AU - Zhang, Lin

AU - Dang, Chi V.

PY - 2022/10/18

Y1 - 2022/10/18

N2 - We identify ADIRF-AS1 circadian long non-coding RNA (lncRNA). Deletion of ADIRF-AS1 in U2OS cells alters rhythmicity of clock-controlled genes and expression of extracellular matrix genes. ADIRF-AS1 interacts with all components of the PBAF (PBRM1/BRG1) complex in U2OS cells. Because PBRM1 is a tumor suppressor mutated in over 40% of clear cell renal carcinoma (ccRCC) cases, we evaluate ADIRF-AS1 in ccRCC cells. Reducing ADIRF-AS1 expression in ccRCC cells decreases expression of some PBAF-suppressed genes. Expression of these genes is partially rescued by PBRM1 loss, consistent with ADIRF-AS1 acting in part to modulate PBAF. ADIRF-AS1 expression correlates with survival in human ccRCC, particularly in PBRM1 wild-type, but not mutant, tumors. Loss of ADIRF-AS1 eliminates in vivo tumorigenesis, partially rescued by concurrent loss of PBRM1 only when co-injected with Matrigel, suggesting a PBRM1-independent function of ADIRF-AS1. Our findings suggest that ADIRF-AS1 functions partly through PBAF to regulate specific genes as a BMAL1-CLOCK-regulated, oncogenic lncRNA.

AB - We identify ADIRF-AS1 circadian long non-coding RNA (lncRNA). Deletion of ADIRF-AS1 in U2OS cells alters rhythmicity of clock-controlled genes and expression of extracellular matrix genes. ADIRF-AS1 interacts with all components of the PBAF (PBRM1/BRG1) complex in U2OS cells. Because PBRM1 is a tumor suppressor mutated in over 40% of clear cell renal carcinoma (ccRCC) cases, we evaluate ADIRF-AS1 in ccRCC cells. Reducing ADIRF-AS1 expression in ccRCC cells decreases expression of some PBAF-suppressed genes. Expression of these genes is partially rescued by PBRM1 loss, consistent with ADIRF-AS1 acting in part to modulate PBAF. ADIRF-AS1 expression correlates with survival in human ccRCC, particularly in PBRM1 wild-type, but not mutant, tumors. Loss of ADIRF-AS1 eliminates in vivo tumorigenesis, partially rescued by concurrent loss of PBRM1 only when co-injected with Matrigel, suggesting a PBRM1-independent function of ADIRF-AS1. Our findings suggest that ADIRF-AS1 functions partly through PBAF to regulate specific genes as a BMAL1-CLOCK-regulated, oncogenic lncRNA.

KW - ADIRF-AS1

KW - CP: Cancer

KW - PBAF

KW - ccRCC

KW - circadian rhythm

KW - clock

KW - lncRNA

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JF - Cell Reports

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Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis

Abstract

Keywords

ASJC Scopus subject areas

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