# A long noncoding RNA antagonizes the PBAF complex to promote ccRCC progression

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2021 · $33,126

## Abstract

Project Summary: We discovered that a completely uncharacterized long noncoding RNA (lncRNA) ADIRF-
AS1 binds to the tumor suppressor Polybromo- and BRG1-associated factors-containing (PBAF) chromatin
modifying complex, including the three unique protein components of the PBAF complex: ARID2, BRD7, and
PBRM1. The PBAF complex bromodomain containing protein PBRM1 is mutated in approximately 40% of clear
cell renal carcinoma (ccRCC), where loss of PBRM1 increases proliferation and overall tumor burden. Publicly
available patient data revealed that ADIRF-AS1 is more highly expressed in ccRCC tumors compared to normal
tissues. We overexpressed ADIRF-AS1 in a panel of ccRCC cell lines and found that ADIRF-AS1 overexpression
significantly promoted proliferation only in ccRCC cell lines with wildtype expression of PBAF protein
components. Importantly, we found that overexpression of ADIRF-AS1 decreased protein expression of PBAF
protein components. Next, we sought to identify how ADIRF-AS1 negatively regulates the PBAF complex. We
performed a lncRNA pulldown assay followed by proteomics analysis and found that along with components of
the PBAF complex, ADIRF-AS1 also associates with an E3 ubiquitin ligase TRIM25, which has been shown to
target PBRM1 for proteasomal degradation. We validated that silencing TRIM25 increases PBRM1 expression
and found that proteasome inhibitors rescued decreased expression of PBRM1 after ADIRF-AS1
overexpression. Therefore, I hypothesize that ADIRF-AS1 interacts with the PBAF complex to promote its
degradation by acting as a scaffold for PBRM1 and TRIM25, promoting tumor formation and progression.
To address this hypothesis, we propose two aims to: (1) Determine the role of ADIRF-AS1 expression in PBAF
mediated metabolism and tumorigenesis, and (2) Characterize the mechanism by which ADIRF-AS1 negatively
regulates the PBAF complex through TRIM25 to promote tumorigenesis.

## Key facts

- **NIH application ID:** 10199962
- **Project number:** 5F31CA232551-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Rebekah Brooks
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,126
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199962

## Citation

> US National Institutes of Health, RePORTER application 10199962, A long noncoding RNA antagonizes the PBAF complex to promote ccRCC progression (5F31CA232551-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10199962. Licensed CC0.

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