Evidence map›Paper›PMID 41639843›Full record

ArticleJournal of translational medicine2026

Targeting miR-4653-3p/SLC25A51/SIRT3 axis to induce synthetic lethality in ARID1A-deficient colorectal cancer via blockade of DNA repair.

Xin Lin, Changjie Wu, Danzhu Wu, Wenjie Qin, Yingyi Zeng, Yixian Song, Li Xiang, Joong Sup Shim, Side Liu, Aimin Li

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PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

10 authors.

Xin LinGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Changjie WuGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Danzhu WuGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Wenjie QinGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Yingyi ZengGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Yixian SongGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Li XiangDepartment of Gastroenterology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, China.
Joong Sup ShimCancer Centre, Faculty of Health Sciences, MOE Frontiers Science Centre for Precision Oncology, University of Macau, Taipa, Macau SAR, China. jsshim@um.edu.mo.
Side LiuGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China. sideliu@smu.edu.cn.
Aimin LiGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China. lam0725@smu.edu.cn.

Funding

Basic and Applied Basic Research Foundation of Guangdong Province 2021A1515111179Basic and Applied Basic Research Foundation of Guangdong Province 2023A1515010280Multi-Year Research Grant of University of Macau MYRG-GRG2024-00056-FHSNational Natural Science Foundation of China 82373165Sanming Project of Medicine in Shenzen Municipality SZSM202105017Science and Technology Development Fund of Macao S.A.R FDCT/0139/2024/AFJScience and Technology Projects in Guangzhou 202201010877Science, Technology and Innovation Commission of Shenzhen Municipality SGDX20220530111004031
6 · The paper itself

Abstract

backgroundARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions as a tumor suppressor and is frequently inactivated across various cancer types. Consequently, ARID1A deficiency has emerged as a promising therapeutic target.

methodsIn this study, we conducted a high-throughput screening of a microRNA (miRNA) mimic library using ARID1A isogenic colorectal cancer (CRC) cell lines and identified a synthetic lethal interaction between ARID1A and miR-4653-3p.

resultsMiR-4653-3p selectively inhibited the proliferation of ARID1A-deficient CRC cells. Mechanistically, miR-4653-3p directly targets SLC25A51, a mitochondrial NAD⁺ transporter gene, leading to impaired SIRT3 enzymatic activity. Since both ARID1A and SIRT3 play critical roles in DNA damage repair, their concurrent loss exacerbates DNA damage accumulation and promotes apoptosis.

conclusionsIn conclusion, our findings reveal a novel synthetic lethality between ARID1A and miR-4653-3p, and suggest that targeting the miR-4653-3p/SLC25A51/SIRT3 axis, in combination with agents that disrupt DNA damage response, may offer a promising therapeutic strategy for ARID1A-deficient CRC.

Indexed as

Colorectal NeoplasmsDNA RepairMicroRNAsSirtuin 3Synthetic Lethal MutationsTranscription FactorsApoptosisBase SequenceCell Line, TumorCell ProliferationDNA-Binding ProteinsGene Expression Regulation, NeoplasticHumansARID1A protein, humanDNA-Binding ProteinsMicroRNAsSIRT3 protein, humanSirtuin 3Transcription FactorsARID1AColorectal cancerDNA damage responsemiR-4653-3pSIRT3SLC25A51Synthetic lethality

Identifiers

PMID41639843
PMCPMC12958540

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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.