Evidence map›Paper›PMID 33082558›Full record

ArticleOncogene2021

MITF is a driver oncogene and potential therapeutic target in kidney angiomyolipoma tumors through transcriptional regulation of CYR61.

Mahsa Zarei, Krinio Giannikou, Heng Du, Heng-Jia Liu, Melissa Duarte, Sneha Johnson, Amin H Nassar, Hans R Widlund, Elizabeth P Henske, Henry W Long and 1 more

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

Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 20 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

11 authors at 3 institutions in 1 country.

Mahsa Zarei *Cancer Genetics Laboratory, Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Krinio Giannikou *Cancer Genetics Laboratory, Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Heng DuCancer Genetics Laboratory, Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9067-0910
Heng-Jia LiuPulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9685-6572
Melissa DuarteCenter for Functional Cancer Epigenetics, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Sneha JohnsonDepartment of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Amin H NassarCancer Genetics Laboratory, Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8084-9105
Hans R WidlundDepartment of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Elizabeth P HenskePulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Henry W LongCenter for Functional Cancer Epigenetics, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6849-6629
David J KwiatkowskiCancer Genetics Laboratory, Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. dk@rics.bwh.harvard.edu.ORCID http://orcid.org/0000-0002-5668-5219
Brigham and Women's Hospital · USHarvard University · USTexas A&M University · US

Funding

Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
NCI NIH HHS P01 CA120964
6 · The paper itself

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor syndrome, characterized by tumor development in multiple organs, including renal angiomyolipoma. Biallelic loss of TSC1 or TSC2 is a known genetic driver of angiomyolipoma development, however, whether an altered transcriptional repertoire contributes to TSC-associated tumorigenesis is unknown. RNA-seq analyses showed that MITF A isoform (MITF-A) was consistently highly expressed in angiomyolipoma, immunohistochemistry showed microphthalmia-associated transcription factor nuclear localization, and Chromatin immuno-Precipitation Sequencing analysis showed that the MITF-A transcriptional start site was highly enriched with H3K27ac marks. Using the angiomyolipoma cell line 621-101, MITF knockout (MITF.KO) and MITF-A overexpressing (MITF.OE) cell lines were generated. MITF.KO cells showed markedly reduced growth and invasion in vitro, and were unable to form xenografted tumors. In contrast, MITF.OE cells grew faster in vitro and as xenografted tumors compared to control cells. RNA-Seq analysis showed that both ID2 and Cysteine-rich angiogenic inducer 61 (CYR61) expression levels were increased in the MITF.OE cells and reduced in the MITF.KO cells, and luciferase assays showed this was due to transcriptional effects. Importantly, CYR61 overexpression rescued MITF.KO cell growth in vitro and tumor growth in vivo. These findings suggest that MITF-A is a transcriptional oncogenic driver of angiomyolipoma tumor development, acting through regulation of CYR61.

Indexed as

Up-RegulationAngiomyolipomaAnimalsCell Line, TumorCell NucleusCell ProliferationCysteine-Rich Protein 61Gene Expression Regulation, NeoplasticGene Knockout TechniquesHumansInhibitor of Differentiation Protein 2Kidney NeoplasmsMiceMicrophthalmia-Associated Transcription FactorNeoplasm InvasivenessNeoplasm TransplantationCCN1 protein, humanCysteine-Rich Protein 61ID2 protein, humanInhibitor of Differentiation Protein 2Microphthalmia-Associated Transcription FactorMITF protein, humanRNA Isoforms

Identifiers

PMID33082558
PMCPMC7796905
OpenAlexW3093721121

What OpenQuestion holds

Textmetadata
LicenceTDM
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.