Evidence map›Paper›PMID 37775817›Full record

ArticleJournal of experimental & clinical cancer research : CR2023

ATR-binding lncRNA ScaRNA2 promotes cancer resistance through facilitating efficient DNA end resection during homologous recombination repair.

Yuanyuan Chen, Hui Shen, Tingting Liu, Kun Cao, Zhijie Wan, Zhipeng Du, Hang Wang, Yue Yu, Shengzhe Ma, Edward Lu and 4 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

9 citing papers in PubMed, 10 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

14 authors at 5 institutions in 1 country.

Yuanyuan Chen *Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
Hui Shen *Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
Tingting Liu *Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
Kun CaoDepartment of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
Zhijie WanDepartment of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
Zhipeng DuSchool of Public Health and Management, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, China.
Hang WangDepartment of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
Yue YuDepartment of Colorectal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Shengzhe MaDepartment of Colorectal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Edward LuDepartment of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
Wei ZhangDepartment of Colorectal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China. weizhang2000cn@163.com.
Jianming CaiSchool of Public Health and Management, Wenzhou Medical University, University Town, Wenzhou, Zhejiang, China. caijianming882003@aliyun.com.
Fu GaoDepartment of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China. gaofusmmu@163.com.
Yanyong YangDepartment of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China. yyyang2010@163.com.
Naval University of Engineering · CNSecond Military Medical University · CNWenzhou Medical University · CNChanghai Hospital · CNJiaxing University · CN

Funding

National Natural Science Foundation of China 81972968National Natural Science Foundation of China 82103776Shanghai Municipal Health Commission No.20214Y0012the Project of South Zhejiang Institute of Radiation Medicine and Nuclear Technology No.ZFY-2021-K-002Three-Year Plan of Shanghai Municipal Health Commission GWV-10.2-YQ27Zhejiang Provincial Natural Science Foundation of Chinae LQ23H220001
6 · The paper itself

Abstract

backgroundOur previous study first showed that ATR-binding long noncoding RNA (lncRNA) is necessary for ATR function and promotes cancer resistance. However, the specific lncRNAs instrumental in ATR activation remain largely unclear, which limits our comprehensive understanding of this critical biological process.

methodsRNA immunoprecipitation (RIP) followed by RNA sequencing was employed to identify ATR-binding lncRNAs, which were further validated using RIP-qPCR assays. Immunofluorescence staining and Western blotting were applied to detect the activation of DNA damage repair factors. After the effect of scaRNA2 on cellular sensitivity to DNA-damaging reagents was determined, the effects of scaRNA2 on radiotherapy were investigated in patient-derived organoids and xenograft preclinical models. The clinical relevance of scaRNA2 was also validated in tissues isolated from rectal cancer patients.

resultsScaRNA2 was identified as the most enriched ATR-binding lncRNA and was found to be essential for homologous recombination (HR) mediated DNA damage repair. Furthermore, scaRNA2 knockdown abrogated the recruitment of ATR and its substrates in response to DNA damage. Mechanistically, scaRNA2 was observed to be necessary for Exo1-mediated DNA end resection and bridged the MRN complex to ATR activation. Knockdown of scaRNA2 effectively increased the sensitivity of cancer cells to multiple kinds of DNA damage-related chemoradiotherapy. Preclinically, knockdown of scaRNA2 improved the effects of radiotherapy on patient-derived organoids and xenograft models. Finally, an increase in scaRNA2 colocalized with ATR was also found in clinical patients who were resistant to radiotherapy.

conclusionsScaRNA2 was identified as the most abundant lncRNA bound to ATR and was demonstrated to bridge DNA end resection to ATR activation; thus, it could be applied as a potent target for combined cancer treatments with chemoradiotherapy.

Indexed as

NeoplasmsRNA, Long NoncodingAtaxia Telangiectasia Mutated ProteinsDNADNA DamageDNA RepairHumansRecombinational DNA RepairAtaxia Telangiectasia Mutated ProteinsATR protein, humanDNARNA, Long NoncodingATRCancer resistanceDNA end resectionScaRNA2

Identifiers

PMID37775817
PMCPMC10542231
OpenAlexW4387160207

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.