Evidence map›Paper›PMID 34544449›Full record

ArticleJournal of experimental & clinical cancer research : CR2021

RNA m6A demethylase FTO-mediated epigenetic up-regulation of LINC00022 promotes tumorigenesis in esophageal squamous cell carcinoma.

Yuanbo Cui, Chunyan Zhang, Shanshan Ma, Zhe Li, Wenjie Wang, Ya Li, Yingchao Ma, Jiarui Fang, Yaping Wang, Wei Cao and 1 more

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

Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
11.8field-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

105 citing papers in PubMed, 169 citations in OpenAlex.

  1. Review
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  6. Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026
    Review
  7. Rewriting the RNA code: an mFrontiers in immunology · 2026
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45 more citing papers are in PubMed but not listed here.

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

11 authors at 2 institutions in 1 country.

Yuanbo CuiSchool of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China. cuiyuanbo18@gs.zzu.edu.cn.
Chunyan ZhangDepartment of Clinical Laboratory, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, China.
Shanshan MaSchool of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Zhe LiSchool of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Wenjie WangSchool of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Ya LiSchool of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Yingchao MaSchool of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Jiarui FangSchool of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Yaping WangSchool of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Wei CaoTranslational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, China. caowei7@zzu.edu.cn.
Fangxia GuanSchool of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China. guanfx@zzu.edu.cn.
Zhengzhou University · CNZhengzhou Central Hospital · CN

Funding

Central Plains Thousand People Plan of Henan Province 204200510013Discipline Innovation and Wisdom Introduction Plan of Higher Education in Henan Province CXJD2021002Key Discipline Construction Project for Prevention and Treatment of Esophageal Cancer in Zhengzhou University XKZDJC202001key programme U2004201science and technology department, henan province SBGJ202003053science and technology department of henan province LHGJ20191054science and technology department of henan province LHGJ20200765, SB201903032
6 · The paper itself

Abstract

backgroundLong non-coding RNA (LncRNA) controls cell proliferation and plays a significant role in the initiation and progression of esophageal squamous cell carcinoma (ESCC). N6-methyladenosine (m6A) modification now is recognized as a master driver of RNA function to maintain homeostasis in cancer cells. However, how m6A regulates LncRNA function and its role in tumorigenesis of ESCC remain unclear.

methodsMultiple ESCC datasets were used to analyze gene expression in tumor tissues and normal tissues. Kaplan-Meier method and the ROC curve were conducted to evaluate the prognostic value and diagnostic value of LINC00022 in ESCC, respectively. Both gain-of-function and loss-of-function experiments were employed to investigate the effects of LINC00022 on ESCC growth in vitro and in vivo. Bioinformatics analysis, colorimetric m6A assay, RIP, MeRIP and co-IP was performed to explore the epigenetic mechanism of LINC00022 up-regulation in ESCC.

resultsHere we report that m6A demethylation of LncRNA LINC00022 by fat mass and obesity-associated protein (FTO) promotes tumor growth of ESCC in vivo. Clinically, we revealed that LINC00022 was up-regulated in primary ESCC samples and was predictive of poor clinical outcome for ESCC patients. Mechanistically, LINC00022 directly binds to p21 protein and promotes its ubiquitination-mediated degradation, thereby facilitating cell-cycle progression and proliferation. Further, the elevated FTO in ESCC decreased m6A methylation of LINC00022 transcript, leading to the inhibition of LINC00022 decay via the m6A reader YTHDF2. Over-expression of FTO was shown to drive LINC00022-dependent cell proliferation and tumor growth of ESCC.

conclusionsThus, this study demonstrated m6A-mediated epigenetic modification of LncRNA contributes to the tumorigenesis in ESCC and LINC00022, specific target of m6A, serves as a potential biomarker for this malignancy.

Indexed as

Gene Expression Regulation, NeoplasticAlpha-Ketoglutarate-Dependent Dioxygenase FTOAnimalsCell Line, TumorCell Transformation, NeoplasticDisease Models, AnimalDNA MethylationEpigenesis, GeneticEsophageal Squamous Cell CarcinomaGene Expression ProfilingHeterograftsHumansMaleMiceRNA, Long NoncodingRNA, MessengerAlpha-Ketoglutarate-Dependent Dioxygenase FTOFTO protein, humanRNA, Long NoncodingRNA, MessengerCell cycleEsophageal squamous cell carcinomaFTOLINC00022N6-methyladenosineTumorigenesis

Identifiers

PMID34544449
PMCPMC8451109
OpenAlexW3200441599

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.