Evidence map›Paper›PMID 25884434›Full record

ArticleBMC cancer2015

HNRNP G and HTRA2-BETA1 regulate estrogen receptor alpha expression with potential impact on endometrial cancer.

Marc Hirschfeld, Yi Qin Ouyang, Markus Jaeger, Thalia Erbes, Marzenna Orlowska-Volk, Axel Zur Hausen, Elmar Stickeler

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

25 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

7 authors at 2 institutions in 2 countries.

Marc HirschfeldDepartment of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr 55, 79106, Freiburg, Germany. marc.hirschfeld@uniklinik-freiburg.de.
Yi Qin OuyangDepartment of Obstetrics and Gynecology, Tongji Hospital of Tongji University, Shanghai, China. oyy91124@hotmail.com.
Markus JaegerDepartment of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr 55, 79106, Freiburg, Germany. markus.jaeger@uniklinik-freiburg.de.
Thalia ErbesDepartment of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr 55, 79106, Freiburg, Germany. thalia.erbes@uniklinik-freiburg.de.
Marzenna Orlowska-VolkInstitute of Pathology, University Medical Center Freiburg, Freiburg, Germany. marzenna.orlowska-volk@uniklinik-freiburg.de.
Axel Zur HausenInstitute of Pathology, University Medical Center Freiburg, Freiburg, Germany. axel.zurhausen@mumc.nl.
Elmar StickelerDepartment of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr 55, 79106, Freiburg, Germany. elmar.stickeler@uniklinik-freiburg.de.
University Medical Center Freiburg · DETongji Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEstrogen receptor alpha (ERa/ESR1) expression is regulated by alternative splicing. Its most frequently detectable exon7 skipping isoform (ERaD7) is a dominant negative variant. Elevated expression of ERaD7 was already detected in endometrial cancer (EC), while its potential prognostic significance has not been characterized so far. Exon7 contains potential binding sites for the two functional splicing regulatory opponents, HNRNPG and HTRA2-BETA1 known to trigger opposite effects on EC outcome. This study served to elucidate the influence of HNRNPG and HTRA2-BETA1 on ERa exon7 splicing regulation and the impact of ERaD7 concentration on type 1 EC outcome.

methodsFunctional in vitro experiments for HNRNPG and HTRA2-BETA1 in regard to the regulatory impact on endogenous and exogenous ERaD7 splicing were performed. Additionally, real-time PCR determined mRNA levels of ERaD7, HNRNPG and HTRA2-BETA1 in 116 type 1 EC patients.

resultsHNRNPG and HTRA2-BETA1 were found to be specific regulators of ERa exon7 splicing. While HTRA2-BETA1 promoted exon7 inclusion, HNRNPG antagonized this effect by inducing exon7 skipping (p = 0.004). ERaD7 was detected in 71 out of 116 type 1 EC specimens. Statistical analyses revealed an inverse correlation between ERaD7 mRNA levels and tumor grading (p = 0.029), FIGO stage (p = 0.033) as well as lymph node metastases (p = 0.032), respectively. Furthermore, higher ERaD7 expression could be correlated to an improved disease-specific survival (p = 0.034).

conclusionsOur study demonstrates antagonistic regulatory effects of HNRNPG and HTRA2-BETA1 on ERa exon7 splicing with potential impact on type 1 EC clinical outcome due to the consecutively variable expression levels of the ERa isoform D7.

Indexed as

Alternative SplicingBinding SitesCell Line, TumorEndometrial NeoplasmsEstrogen Receptor alphaExonsFemaleHeLa CellsHeterogeneous-Nuclear RibonucleoproteinsHumansNerve Tissue ProteinsPrognosisRNA-Binding ProteinsSerine-Arginine Splicing FactorsESR1 protein, humanEstrogen Receptor alphaHeterogeneous-Nuclear RibonucleoproteinsNerve Tissue ProteinsRBMX protein, humanRNA-Binding ProteinsSerine-Arginine Splicing FactorsTRA2B protein, human

Identifiers

PMID25884434
PMCPMC4355463
OpenAlexW2148563070

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.