Evidence map›Paper›PMID 22689922›Full record

ArticleCarcinogenesis2012

Dysregulation of miR-31 and miR-21 induced by zinc deficiency promotes esophageal cancer.

Hansjuerg Alder, Cristian Taccioli, Hongping Chen, Yubao Jiang, Karl J Smalley, Paolo Fadda, Hatice G Ozer, Kay Huebner, John L Farber, Carlo M Croce and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Carcinogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 2 pooled it
4.9field-weighted citation impact, top 4% 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

66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.

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  10. Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2023
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6 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 3 institutions in 2 countries.

Hansjuerg AlderDepartment of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University Columbus, OH 43210, USA.
Cristian Taccioli
Hongping Chen
Yubao Jiang
Karl J Smalley
Paolo Fadda
Hatice G Ozer
Kay Huebner
John L Farber
Carlo M Croce
Louise Y Y Fong
The Ohio State University · USThomas Jefferson University · USSidney Kimmel Cancer Center · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
The Role of Epigenetic Factors in Regulation of Coding and Non-Coding HOX GenesP01CA129242 · NCI · OHIO STATE UNIVERSITY · PI CROCE, CARLO M · 2009 to 2013
$4.7M
Chemoprevention of upper aerodigestive tract cancer by dietary zincR01CA118560 · NCI · THOMAS JEFFERSON UNIVERSITY · PI FONG, LOUISE Y.Y. · 2006 to 2017
$2.7M
FHIT Gene Therapy in Cancer Prevention and TreatmentR01CA115965 · NCI · OHIO STATE UNIVERSITY · PI CROCE, CARLO M · 2007 to 2011
$1.1M
Modulation of miR-31 by dietary zinc deficiency in rat esophageal carcinogenesisR21CA152505 · NCI · THOMAS JEFFERSON UNIVERSITY · PI FONG, LOUISE Y.Y. · 2011 to 2012
$371k
NCI NIH HHS P01 CA129242NCI NIH HHS P30 CA016058NCI NIH HHS R01CA115965NCI NIH HHS R01 CA118560NCI NIH HHS R01CA118560NCI NIH HHS R21 CA152505NCI NIH HHS R21CA152505
6 · The paper itself

Abstract

Zinc deficiency (ZD) increases the risk of esophageal squamous cell carcinoma (ESCC). In a rat model, chronic ZD induces an inflammatory gene signature that fuels ESCC development. microRNAs regulate gene expression and are aberrantly expressed in cancers. Here we investigated whether chronic ZD (23 weeks) also induces a protumorigenic microRNA signature. Using the nanoString technology, we evaluated microRNA profiles in ZD esophagus and six additional tissues (skin, lung, pancreas, liver, prostate and peripheral blood mononuclear cells [PBMC]). ZD caused overexpression of inflammation genes and altered microRNA expression across all tissues analyzed, predictive of disease development. Importantly, the inflammatory ZD esophagus had a distinct microRNA signature resembling human ESCC or tongue SCC miRNAomes with miR-31 and miR-21 as the top-up-regulated species. Circulating miR-31 was also the top-up-regulated species in PBMCs. In ZD esophagus and tongue, oncogenic miR-31 and miR-21 overexpression was accompanied by down-regulation of their respective tumor-suppressor targets PPP2R2A and PDCD4. Importantly, esophageal miR-31 and miR-21 levels were directly associated with the appearance of ESCC in ZD rats, as compared with their cancer-free Zn-sufficient or Zn-replenished counterparts. In situ hybridization analysis in rat and human tongue SCCs localized miR-31 to tumor cells and miR-21 to stromal cells. In regressing tongue SCCs from Zn-supplemented rats, miR-31 and miR-21 expression was concomitantly reduced, establishing their responsiveness to Zn therapy. A search for putative microRNA targets revealed a bias toward genes in inflammatory pathways. Our finding that ZD causes miR-31 and miR-21 dysregulation associated with inflammation provides insight into mechanisms whereby ZD promotes ESCC.

Indexed as

AnimalsApoptosis Regulatory ProteinsCarcinoma, Squamous CellEsophageal NeoplasmsEsophagusHumansMaleMicroRNAsRatsRats, Sprague-DawleyRNA-Binding ProteinsTongueTongue NeoplasmsZincApoptosis Regulatory ProteinsMicroRNAsMIRN21 microRNA, humanMIRN31 microRNA, humanPDCD4 protein, humanRNA-Binding ProteinsZinc

Identifiers

PMID22689922
PMCPMC3514898
OpenAlexW2135858383

What OpenQuestion holds

Textmetadata
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.