Evidence map›Paper›PMID 32653028›Full record

ArticleJournal of experimental & clinical cancer research : CR2020

LncRNA HOTAIR-mediated MTHFR methylation inhibits 5-fluorouracil sensitivity in esophageal cancer cells.

Shuyao Zhang, Fuchun Zheng, Liqun Zhang, Zuojun Huang, Xiaoshan Huang, Zhen Pan, Shuang Chen, Chenchen Xu, Yi Jiang, Shuyi Gu and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. International journal of molecular medicine · 2026
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  20. Targeting purine metabolism in ovarian cancer.Journal of ovarian research · 2022
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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

13 authors at 5 institutions in 1 country.

Shuyao ZhangDepartment of Pharmacology, Shantou University Medical College, Shantou, 515041, P.R. China.
Fuchun ZhengPharmaceutical Laboratory, The First Affiliated Hospital, Shantou University Medical College, Shantou, 515041, P.R. China.
Liqun ZhangInformation Section, Cancer Hospital of Shantou University Medical College, Shantou, 515031, P.R. China.
Zuojun HuangDepartment of Pharmacology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, 510220, P.R. China.
Xiaoshan HuangDepartment of Pharmacology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, 510220, P.R. China.
Zhen PanDepartment of Pharmacology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, 510220, P.R. China.
Shuang ChenDepartment of Pharmacology, Shantou University Medical College, Shantou, 515041, P.R. China.
Chenchen XuDepartment of Pharmacology, Shantou University Medical College, Shantou, 515041, P.R. China.
Yi JiangDepartment of Digestive Oncology, Cancer Hospital of Shantou University Medical College, Shantou, 515031, P.R. China.
Shuyi GuDepartment of Pharmacology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, 510220, P.R. China.
Chengkuan ZhaoDepartment of Pharmacology, Shantou University Medical College, Shantou, 515041, P.R. China.
Qiuzhen ZhangDepartment of Pharmacology, Shantou University Medical College, Shantou, 515041, P.R. China.
Ganggang ShiDepartment of Pharmacology, Shantou University Medical College, Shantou, 515041, P.R. China. ggshi@stu.edu.cn.
Jinan University · CNShantou University · CNCancer Hospital of Shantou University Medical College · CNFirst Affiliated Hospital of Shantou University Medical College · CNShantou University Medical College · CN

Funding

Dedicated Fund for Tumor-Targeting of Wu Jieping Medical Foundation Project ID: 320.6750.19090-2the Letter from the Third Batch and Fourth Batch of Medical and Health Science and Technology Program Project Funds in Shantou City in 2018 Shan Fu Ke letter (2018) 238
6 · The paper itself

Abstract

backgroundEsophageal cancer (EC) represents one of the most aggressive digestive neoplasms globally, with marked geographical variations in morbidity and mortality. Chemoprevention is a promising approach for cancer therapy, while acquired chemoresistance is a major obstacle impeding the success of 5-fluorouracil (5-FU)-based chemotherapy in EC, with the mechanisms underlying resistance not well-understood. In the present study, we focus on exploring the role of long non-coding RNA (lncRNA) HOTAIR in EC progression and sensitivity of EC cells to 5-FU.

methodsPaired cancerous and pre-cancerous tissues surgically resected from EC patients were collected in this study. Promoter methylation of the MTHFR was assessed by methylation-specific PCR. RIP and ChIP assays were adopted to examine the interaction of DNA methyltransferases (DNMTs) with lncRNA HOTAIR and MTHFR, respectively. EC cells resistant to 5-FU were induced by step-wise continuous increasing concentrations of 5-FU. The sensitivity of EC cells to 5-FU in vivo was evaluated in nude mice treated with xenografts of EC cells followed by injection with 5-FU (i.p.).

resultsWe found reciprocal expression patterns of lncRNA HOTAIR and MTHFR in EC tissues and human EC cells. Interference with lncRNA HOTAIR enhanced 5-FU-induced apoptosis, exhibited anti-proliferative activity, and reduced promoter methylation of the MTHFR in EC cells. Besides, overexpression of MTHFR attenuated the acquired chemoresistance induced by overexpression of lncRNA HOTAIR in EC cells. At last, enhanced chemosensitivity was observed in vivo once nude mice xenografted with lncRNA HOTAIR-depleted EC cells.

conclusionTogether, our study proposes that pharmacologic targeting of lncRNA HOTAIR sensitizes EC cells to 5-FU-based chemotherapy by attenuating the promoter hypermethylation of the MTHFR in EC.

Indexed as

DNA MethylationDrug Resistance, NeoplasmAnimalsAntimetabolites, AntineoplasticApoptosisBiomarkers, TumorCell ProliferationEsophageal NeoplasmsFluorouracilGene Expression Regulation, NeoplasticHumansMethylenetetrahydrofolate Reductase (NADPH2)MiceMice, NudeMiddle AgedPrognosisAntimetabolites, AntineoplasticBiomarkers, TumorFluorouracilHOTAIR long untranslated RNA, humanMethylenetetrahydrofolate Reductase (NADPH2)MTHFR protein, humanRNA, Long Noncoding5-fluorouracilChemosensitivityEsophageal cancerlncRNA HOTAIRMTHFR

Identifiers

PMID32653028
PMCPMC7353690
OpenAlexW3040932118

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.