Evidence map›Paper›PMID 38503731›Full record

ArticleCell discovery2024

RBBP6 maintains glioblastoma stem cells through CPSF3-dependent alternative polyadenylation.

Peng Lin, Wenyan Chen, Zhilin Long, Jichuan Yu, Jiayao Yang, Zhen Xia, Qiulian Wu, Xinyu Min, Jing Tang, Ya Cui and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cell discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
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

13 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 2 countries.

Peng Lin *College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Wenyan Chen *Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
Zhilin LongWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
Jichuan YuWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
Jiayao YangWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
Zhen XiaWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
Qiulian WuUniversity of Pittsburgh Medical Center Hillman Cancer Center, Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
Xinyu MinWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
Jing TangKey Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Ya CuiDivision of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0003-1574-0928
Fuyi LiuDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Chun WangDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Jian ZhengDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Wei LiDivision of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0001-9931-5990
Jeremy N RichUniversity of Pittsburgh Medical Center Hillman Cancer Center, Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA. drjeremyrich@gmail.com.ORCID http://orcid.org/0000-0001-7845-5302
Lei LiShenzhen Bay Laboratory, Shenzhen, Guangdong, China. lei.li@szbl.ac.cn.ORCID http://orcid.org/0000-0003-3924-2544
Qi XieWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China. xieqi@westlake.edu.cn.ORCID http://orcid.org/0000-0002-2370-2078
Westlake University · CNSecond Affiliated Hospital of Zhejiang University · CNShenzhen Bay Laboratory · CNUniversity of California, Irvine · USUPMC Hillman Cancer Center · US

Funding

Dynamic Complexity of Brain Tumor Stem Cells (R35CA197718)R35CA197718 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2015 to 2021
$6.4M
Targeting the Circadian Rhythm in Glioblastoma Stem Cells (R01CA238662)R01CA238662 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAY, STEVE A, RICH, JEREMY N · 2020 to 2024
$2.8M
National Natural Science Foundation of China (National Science Foundation of China) 32100533National Natural Science Foundation of China (National Science Foundation of China) 82073268U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA197718U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA238662U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) NS103434
6 · The paper itself

Abstract

Glioblastoma is one of the most lethal malignant cancers, displaying striking intratumor heterogeneity, with glioblastoma stem cells (GSCs) contributing to tumorigenesis and therapeutic resistance. Pharmacologic modulators of ubiquitin ligases and deubiquitinases are under development for cancer and other diseases. Here, we performed parallel in vitro and in vivo CRISPR/Cas9 knockout screens targeting human ubiquitin E3 ligases and deubiquitinases, revealing the E3 ligase RBBP6 as an essential factor for GSC maintenance. Targeting RBBP6 inhibited GSC proliferation and tumor initiation. Mechanistically, RBBP6 mediated K63-linked ubiquitination of Cleavage and Polyadenylation Specific Factor 3 (CPSF3), which stabilized CPSF3 to regulate alternative polyadenylation events. RBBP6 depletion induced shortening of the 3'UTRs of MYC competing-endogenous RNAs to release miR-590-3p from shortened UTRs, thereby decreasing MYC expression. Targeting CPSF3 with a small molecular inhibitor (JTE-607) reduces GSC viability and inhibits in vivo tumor growth. Collectively, RBBP6 maintains high MYC expression in GSCs through regulation of CPSF3-dependent alternative polyadenylation, providing a potential therapeutic paradigm for glioblastoma.

Identifiers

PMID38503731
PMCPMC10951364
OpenAlexW4392963287

What OpenQuestion holds

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Registered trials

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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.