Evidence map›Paper›PMID 38315284›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2024

OTUB1 accelerates hepatocellular carcinoma by stabilizing RACK1 via its non-canonical ubiquitination.

Liqun Peng, Tiangen Wu, Yingyi Liu, Dongli Zhao, Wenzhi He, Yufeng Yuan

Abstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

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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

12 citing papers in PubMed.

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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

6 authors.

Liqun PengDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Tiangen WuDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Yingyi LiuDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Dongli ZhaoCollege of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan, China.
Wenzhi HeDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China. hewz@whu.edu.cn.
Yufeng YuanDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China. yuanyf1971@whu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDysregulated ubiquitination modification occupies a pivotal role in hepatocellular carcinoma (HCC) tumorigenesis and progression. The ubiquitin aldehyde binding 1 (OTUB1) was aberrantly upregulated and exhibited the pro-tumorigenic function in HCC. However, the underlying mechanisms and responsible targets of OTUB1 remain unclear.

methodsFirst, bioinformatics analysis, western blot and immunohistochemistry staining were applied to analyze OTUB1 expression in HCC specimens. Then, immunoprecipitation assay-tandem mass spectrometry (MS) combined with the gene set enrichment analysis (GSEA) was used to explore the downstream target of OTUB1. Co-immunoprecipitation and ubiquitination assays were used to identify the mechanisms involved. Finally, we explored the regulatory effect of MAZ on OTUB1 through ChIP-qPCR and dual-luciferase reporter assay.

resultsOTUB1 was broadly elevated in HCC tissues and promoted the proliferation and metastasis of HCC in vitro and in vivo. The receptor for activated C kinase 1 (RACK1) performed as a functional partner of OTUB1 and its hyperactivation was associated with aggressive development and other malignant features in HCC by activating oncogenes transcription. Mechanistically, OTUB1 directly bound to RACK1 at its C-terminal domain and decreased the K48-linked ubiquitination of RACK1 through its non-canonical suppression of ubiquitination activity, which stabilized RACK1 protein levels in HCC cells. Therefore, OTUB1 significantly increased multiple oncogenes expression and activated PI3K/AKT and FAK/ERK signaling in a RACK1-dependent manner in HCC. Moreover, the transcription factor MAZ upregulated OTUB1 expression through identifying a putative response element of OTUB1 promoter area.

conclusionsOur findings might provide a new therapeutic strategy for HCC by modifying the MAZ-OTUB1-RACK1 axis.

Indexed as

Carcinoma, HepatocellularCell ProliferationLiver NeoplasmsNeoplasm ProteinsReceptors for Activated C KinaseUbiquitinationAnimalsCell Line, TumorCysteine EndopeptidasesDeubiquitinating EnzymesFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, Inbred BALB CCysteine EndopeptidasesDeubiquitinating EnzymesNeoplasm ProteinsOTUB1 protein, humanRACK1 protein, humanReceptors for Activated C KinaseUbiquitin-Specific ProteasesHepatocellular carcinomaOTUB1PI3K/AKT signaling pathwayRACK1Ubiquitination

Identifiers

PMID38315284
PMCPMC11219430

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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.