Evidence map›Paper›PMID 36357365›Full record

ArticleCell death & disease2022

Inhibition of USP1 activates ER stress through Ubi-protein aggregation to induce autophagy and apoptosis in HCC.

Longhao Wang, Tao Hu, Zhibo Shen, Yuanyuan Zheng, Qishun Geng, Lifeng Li, Beibei Sha, Miaomiao Li, Yaxin Sun, Yongjun Guo and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

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  19. Deubiquitylating Enzymes in Hepatocellular Carcinoma.International journal of biological sciences · 2025
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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

14 authors at 2 institutions in 1 country.

Longhao Wang *Internet Medical and System, Applications of National Engineering Laboratory, The First Afliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Tao Hu *Academy of Medical Sciences, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Zhibo ShenInternet Medical and System, Applications of National Engineering Laboratory, The First Afliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Yuanyuan ZhengInternet Medical and System, Applications of National Engineering Laboratory, The First Afliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Qishun GengInternet Medical and System, Applications of National Engineering Laboratory, The First Afliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Lifeng LiInternet Medical and System, Applications of National Engineering Laboratory, The First Afliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Beibei ShaAcademy of Medical Sciences, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Miaomiao LiAcademy of Medical Sciences, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Yaxin SunAcademy of Medical Sciences, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Yongjun GuoThe Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, No 127, Dongming Road, Zhengzhou, Henan, 450008, China.
Wenhua XueDepartment of Pharmacy, The First Afliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Dan XuanExperimental animal center of Zhengzhou University, Zhengzhou, China.
Ping ChenAcademy of Medical Sciences, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China. zzdx_chenping@zzu.edu.cn.ORCID 0000-0002-8504-5552
Jie ZhaoInternet Medical and System, Applications of National Engineering Laboratory, The First Afliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. zhaojie@zzu.edu.cn.ORCID 0000-0003-1168-8384
First Affiliated Hospital of Zhengzhou University · CNZhengzhou University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The deubiquitinating enzyme USP1 (ubiquitin-specific protease 1) plays a role in the progression of various tumors, emerging as a potential therapeutic target. This study aimed to determine the role of USP1 as a therapeutic target in hepatocellular carcinoma (HCC). We detected USP1 expression in the tumor and adjacent tissues of patients with HCC using immunohistochemical staining. We evaluated the effect of the USP1 inhibitor ML-323 on HCC cell proliferation and cell cycle using a CCK-8 cell-counting kit and plate cloning assays, and propidium iodide, respectively. Apoptosis was detected by annexin V-FITC/Propidium Iodide (PI) staining and caspase 3 (casp3) activity. Transmission electron microscopy and LC3B immunofluorescence were used to detect autophagy. Western blotting was used to detect the accumulation of ubiquitinated proteins, the expression of endoplasmic reticulum (ER) stress-related proteins, and the AMPK-ULK1/ATG13 signaling pathway. We demonstrated that ML-323 inhibits the growth of HCC cells and induces G1 phase cell cycle arrest by regulating cyclin expression. ML-323 treatment resulted in the accumulation of ubiquitinated proteins, induced ER stress, and triggered Noxa-dependent apoptosis, which was regulated by the Activating Transcription Factor 4(ATF4). Moreover, active ER stress induces protective autophagy by increasing AMPK phosphorylation; therefore, we inhibited ER stress using 4-Phenylbutyric acid (4-PBA), which resulted in ER stress reduction, apoptosis, and autophagy in ML-323-treated HCC cells. In addition, blocking autophagy using the AMPK inhibitor compound C (CC), chloroquine (CQ), or bafilomycin A1 (BafA1) enhanced the cytotoxic effect of ML-323. Our findings revealed that targeting USP1 may be a potential strategy for the treatment of HCC.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsAMP-Activated Protein KinasesApoptosisAutophagyCell Line, TumorEndoplasmic Reticulum StressHumansPropidiumProtein AggregatesUbiquitinated ProteinsUbiquitin-Specific ProteasesAMP-Activated Protein KinasesPropidiumProtein AggregatesUbiquitinated ProteinsUbiquitin-Specific ProteasesUSP1 protein, human

Identifiers

PMID36357365
PMCPMC9649627
OpenAlexW4309075680

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.