Evidence map›Paper›PMID 36052492›Full record

ArticleCancer research2022

Gain of Chromosome 1q Perturbs a Competitive Endogenous RNA Network to Promote Melanoma Metastasis.

Xiaonan Xu, Kaizhen Wang, Olga Vera, Akanksha Verma, Neel Jasani, Ilah Bok, Olivier Elemento, Dongliang Du, Xiaoqing Yu, Florian A Karreth

Open access · greenAbstract read
In one paragraph

Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

10 citing papers in PubMed, 13 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

10 authors at 3 institutions in 2 countries.

Xiaonan XuDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0002-7366-580X
Kaizhen WangDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0001-6033-7041
Olga VeraDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0002-1878-4945
Akanksha VermaCaryl and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York.
Neel JasaniDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0003-1133-5554
Ilah BokDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
Olivier ElementoCaryl and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York.ORCID 0000-0002-8061-9617
Dongliang DuDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
Xiaoqing YuDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
Florian A KarrethDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0002-2350-9809
Moffitt Cancer Center · USUniversity of South Florida · USCornell University · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
Chromosome 1q ceRNAs in Melanoma Progression and MetastasisR01CA259046 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI KARRETH, FLORIAN · 2021 to 2025
$2.3M
An ESC-GEMM platform for rapid melanoma mouse modelingR03CA227349 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI KARRETH, FLORIAN · 2018 to 2019
$172k
NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA259046NCI NIH HHS R03 CA227349
6 · The paper itself

Abstract

Somatic copy-number alterations (CNA) promote cancer, but the underlying driver genes may not be comprehensively identified if only the functions of the encoded proteins are considered. mRNAs can act as competitive endogenous RNAs (ceRNA), which sponge miRNAs to posttranscriptionally regulate gene expression in a protein coding-independent manner. We investigated the contribution of ceRNAs to the oncogenic effects of CNAs. Chromosome 1q gains promoted melanoma progression and metastasis at least in part through overexpression of three mRNAs with ceRNA activity: CEP170, NUCKS1, and ZC3H11A. These ceRNAs enhanced melanoma metastasis by sequestering tumor suppressor miRNAs. Orthogonal genetic assays with miRNA inhibitors and target site blockers, along with rescue experiments, demonstrated that miRNA sequestration is critical for the oncogenic effects of CEP170, NUCKS1, and ZC3H11A mRNAs. Furthermore, chromosome 1q ceRNA-mediated miRNA sequestration alleviated the repression of several prometastatic target genes. This regulatory RNA network was evident in other cancer types, suggesting chromosome 1q ceRNA deregulation as a common driver of cancer progression. Taken together, this work demonstrates that ceRNAs mediate the oncogenicity of somatic CNAs. SIGNIFICANCE: The function of CEP170, NUCKS1, and ZC3H11A mRNAs as competitive endogenous RNAs that sequester tumor suppressor microRNAs underlies the oncogenic activity of chromosome 1q gains.

Indexed as

MelanomaMicroRNAsRNA, Long NoncodingCarcinogenesisChromosomesGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansRNA, MessengerMicroRNAsRNA, Long NoncodingRNA, Messenger

Identifiers

PMID36052492
PMCPMC9971359
OpenAlexW4285031804

What OpenQuestion holds

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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.