Evidence map›Paper›PMID 38439082›Full record

ArticleJournal of experimental & clinical cancer research : CR2024

MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis.

Xiaobin Wang, Yingqing Shi, Hua Shi, Xiaoyu Liu, Aijun Liao, Zhuogang Liu, Robert Z Orlowski, Rui Zhang, Huihan Wang

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
16.4field-weighted citation impact, top 1% 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

35 citing papers in PubMed, 36 citations in OpenAlex.

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  13. Bulk and single cell RNA sequencing data reveal lactylation-related gene signatures for prognosis and immunity in cervical cancer.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026
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  19. EccDNA-Driven VPS41 Amplification Alleviates Genotoxic Stress via Lysosomal KAI1 Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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

9 authors at 4 institutions in 2 countries.

Xiaobin WangDepartment of Hematology, Shengjing Hospital, China Medical University, Shenyang, China.
Yingqing ShiDepartment of Hematology, Daping Hospital, Chongqing, China.
Hua ShiShenshan Medical Center, Memorial Hospital of Sun Yat-Sen University, Shanwei, China.
Xiaoyu LiuDepartment of Hematology, Shengjing Hospital, China Medical University, Shenyang, China.
Aijun LiaoDepartment of Hematology, Shengjing Hospital, China Medical University, Shenyang, China.
Zhuogang LiuDepartment of Hematology, Shengjing Hospital, China Medical University, Shenyang, China.
Robert Z OrlowskiDepartments of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. rorlowski@mdanderson.org.
Rui ZhangDepartment of Hematology, The First Affiliated Hospital, China Medical University, Shenyang, China. hemozerro2008@hotmail.com.
Huihan WangDepartment of Hematology, Shengjing Hospital, China Medical University, Shenyang, China. wanghh@sj-hospital.org.
China Medical University · CNDaping Hospital · CNSun Yat-sen University · CNThe University of Texas MD Anderson Cancer Center · US

Funding

Natural Science Foundation of Liaoning Province 2022-YGJC-61;2022-MS-219
6 · The paper itself

Abstract

backgroundProteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation.

methodsWe used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and EccDNA-seq in MM cell lines and collected human primary MM samples to explore gene profiles. We evaluated the effect of MUC20 on cuproptosis of PI-resistant MM cells using Co-immunoprecipitation (Co-IP), Seahorse bioenergetic profiling and in vivo assay.

resultsThis study revealed that the downregulation of Mucin 20 (MUC20) could predict PI sensitivity and outcomes in MM patients. Besides, MUC20 attenuated PI resistance in MM cells by inducing cuproptosis via the inhibition of cyclin-dependent kinase inhibitor 2 A expression (CDKN2A), which was achieved by hindering MET proto-oncogene, receptor tyrosine kinase (MET) activation. Moreover, MUC20 suppressed MET activation by repressing insulin-like growth factor receptor-1 (IGF-1R) lactylation in PI-resistant MM cells. This study is the first to perform extrachromosomal circular DNA (eccDNA) sequencing for MM, and it revealed that eccDNA induced PI resistance by amplifying kinesin family member 3 C (KIF3C) to reduce MUC20 expression in MM.

conclusionOur findings indicated that MUC20 regulated by eccDNA alleviates PI resistance of MM by modulating cuproptosis, which would provide novel strategies for the treatment of PI-resistant MM.

Indexed as

Multiple MyelomaProteasome InhibitorsAntiviral AgentsCytoplasmDNADNA, CircularHumansKinesinsMucinsOncogenesAntiviral AgentsDNADNA, CircularKIF3C protein, humanKinesinsMUC20 protein, humanMucinsProteasome InhibitorsCuproptosisEccDNAMUC20Multiple myelomaProteasome inhibitorResistance

Identifiers

PMID38439082
PMCPMC10913264
OpenAlexW4392467984

What OpenQuestion holds

Textmetadata
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.