Evidence map›Paper›PMID 25675535›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Silencing LRH-1 in colon cancer cell lines impairs proliferation and alters gene expression programs.

James R Bayrer, Sridevi Mukkamala, Elena P Sablin, Paul Webb, Robert J Fletterick

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.9field-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

35 citing papers in PubMed, 66 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Nuclear receptor NR5A2 negatively regulates cell proliferation and tumor growth in nervous system malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  9. Mapping of mMolecular cancer research : MCR · 2021
    Article
  10. Article
  11. Article
  12. Review
  13. Frontiers in cell and developmental biology · 2021
    Article
  14. Downregulation ofInternational journal of molecular sciences · 2020
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
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

5 authors at 2 institutions in 1 country.

James R BayrerDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Francisco, CA 94143-0136;
Sridevi MukkamalaDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94158-2517; and.
Elena P SablinDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94158-2517; and.
Paul WebbDepartment of Genomic Medicine, Houston Methodist Research Institute, Houston, TX 77030.
Robert J FletterickDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94158-2517; and robert.fletterick@ucsf.edu.
University of California, San Francisco · USHouston Methodist · US

Funding

TRAINING PROGRAM IN PEDIATRIC GASTROENTEROLOGY/NUTRITIONT32DK007762 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI James Bayrer · 1998 to 2026
$7.3M
Child Health Career Development Program at UCSFK12HD072222 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIERO, DONNA M. · 2013 to 2017
$2.0M
Targeting Intestinal Epithelium to Promote Healing in Inflammatory Bowel DiseaseK08DK106577 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BAYRER, JAMES · 2016 to 2018
$497k
LRH-1: Structure-based Approach to Drug Design for Gastrointestinal TumorsF32CA163092 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BAYRER, JAMES · 2012 to 2013
$77k
NCI NIH HHS F32 CA163092NICHD NIH HHS K12 HD07222NICHD NIH HHS K12 HD072222NIDDK NIH HHS K08 DK106577NIDDK NIH HHS T32 DK007762NIDDK NIH HHS T32DK007762
6 · The paper itself

Abstract

Colorectal cancers (CRCs) account for nearly 10% of all cancer deaths in industrialized countries. Recent evidence points to a central role for the nuclear receptor liver receptor homolog-1 (LRH-1) in intestinal tumorigenesis. Interaction of LRH-1 with the Wnt/β-catenin pathway, highly active in a critical subpopulation of CRC cells, underscores the importance of elucidating LRH-1's role in this disease. Reduction of LRH-1 diminishes tumor burden in murine models of CRC; however, it is not known whether LRH-1 is required for tumorigenesis, for proliferation, or for both. In this work, we address this question through shRNA-mediated silencing of LRH-1 in established CRC cell lines. LRH-1 mRNA knockdown results in significantly impaired proliferation in a cell line highly expressing the receptor and more modest impairment in a cell line with moderate LRH-1 expression. Cell-cycle analysis shows prolongation of G0/G1 with LRH-1 silencing, consistent with LRH-1 cell-cycle influences in other tissues. Cluster analysis of microarray gene expression demonstrates significant genome wide alterations with major effects in cell-cycle regulation, signal transduction, bile acid and cholesterol metabolism, and control of apoptosis. This study demonstrates a critical proproliferative role for LRH-1 in established colon cancer cell lines. LRH-1 exerts its effects via multiple signaling networks. Our results suggest that selected CRC patients could benefit from LRH-1 inhibitors.

Indexed as

Gene Expression Regulation, NeoplasticGene SilencingCaco-2 CellsCell CycleCell ProliferationColonic NeoplasmsGene Knockdown TechniquesHT29 CellsHumansOligonucleotide Array Sequence AnalysisReceptors, Cytoplasmic and NuclearReproducibility of ResultsNR5A2 protein, humannuclear receptor subfamily 0, group B, member 2Receptors, Cytoplasmic and Nuclearcolorectal cancerliver receptor homolog 1LRH-1NR5A2nuclear receptor

Identifiers

PMID25675535
PMCPMC4345603
OpenAlexW2009639026

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.