Evidence map›Paper›PMID 37873389›Full record

ArticlebioRxiv : the preprint server for biology2023

Targeted inhibition of BET proteins in HPV-16 associated head and neck squamous cell carcinoma reveals heterogeneous transcription response.

Aakarsha Rao, Zijian Ni, Dhruthi Suresh, Chitrasen Mohanty, Albert R Wang, Denis L Lee, Kwangok P Nickel, Sooryanarayana Randall J Varambally, Paul F Lambert, Christina Kendziorski and 1 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Aakarsha RaoDepartment of Human Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53705, USA.
Zijian NiDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Dhruthi SureshDepartment of Human Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53705, USA.
Chitrasen MohantyDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Albert R WangDepartment of Human Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53705, USA.
Denis L LeeMcArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
Kwangok P NickelDepartment of Human Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53705, USA.
Sooryanarayana Randall J VaramballyMolecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Paul F LambertMcArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
Christina KendziorskiDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Gopal IyerDepartment of Human Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53705, USA.
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Justine Yang Bruce · 1985 to 2026
$142.6M
Project 3: Modulation of the head and neck tumor immune microenvironment by targeting the TAM family of receptorsP50CA278595 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI David J Beebe · 2022 to 2026
$12.5M
Combining BET protein inhibitors with radiation in HPV oropharyngeal cancerR21CA267518 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI IYER, GOPAL · 2023 to 2024
$379k
NCI NIH HHS P30 CA014520NCI NIH HHS P50 CA278595NCI NIH HHS R21 CA267518
6 · The paper itself

Abstract

Integrated human papillomavirus (HPV-16) associated head and neck squamous cell carcinoma (HNSCC) tumors have worse survival outcomes compared to episomal HPV-16 HNSCC tumors. Therefore, there is a need to differentiate treatment for HPV-16 integrated HNSCC from other viral forms. We analyzed TCGA data and found that HPV+ HNSCC expressed higher transcript levels of the bromodomain and extra terminal domain (BET) family of transcriptional coregulators. However, the mechanism of BET protein-mediated transcription of viral-cellular genes in the integrated viral-HNSCC genomes needs to be better understood. We show that BET inhibition downregulates E6 significantly independent of the viral transcription factor, E2, and there was overall heterogeneity in the downregulation of viral transcription in response to the effects of BET inhibition across HPV-associated cell lines. Chemical BET inhibition was phenocopied with the knockdown of BRD4 and mirrored downregulation of viral E6 and E7 expression. Strikingly, there was heterogeneity in the reactivation of p53 levels despite E6 downregulation, while E7 downregulation did not alter Rb levels significantly. We identified that BET inhibition directly downregulated c-Myc and E2F expression and induced CDKN1A expression. Overall, our studies show that BET inhibition provokes a G1-cell cycle arrest with apoptotic activity and suggests that BET inhibition regulates both viral and cellular gene expression in HPV-associated HNSCC.

Identifiers

PMID37873389
PMCPMC10592929
OpenAlexW4387329224

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.