Evidence map›Paper›PMID 25565142›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2015

Epigenetic regulation of the lncRNA MEG3 and its target c-MET in pancreatic neuroendocrine tumors.

Sita D Modali, Vaishali I Parekh, Electron Kebebew, Sunita K Agarwal

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

Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
11.3field-weighted citation impact, top 1% 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

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Menin in Cancer.Genes · 2024
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Navigating the genomic instability mine field of osteosarcoma to better understand implications of non-coding RNAs.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2022
    Article
  14. Review
  15. Epigenetic regulation of gastrointestinal cancers mediated by long non-coding RNAs.Cancer biomarkers : section A of Disease markers · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

11 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

4 authors at 2 institutions in 1 country.

Sita D ModaliMetabolic Diseases Branch (S.D.M., V.I.P., S.K.A.), National Institute of Diabetes and Digestive and Kidney Diseases, and Endocrine Oncology Branch (E.K.), National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892.
Vaishali I Parekh
Electron Kebebew
Sunita K Agarwal
National Institutes of Health · USNational Institute of Diabetes and Digestive and Kidney Diseases · US

Funding

Genes associated with endocrine tumorigenesisZIADK075035 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI AGARWAL, SUNITA · 2009 to 2025
$6.9M
6 · The paper itself

Abstract

Biallelic inactivation of MEN1 encoding menin in pancreatic neuroendocrine tumors (PNETs) associated with the multiple endocrine neoplasia type 1 (MEN1) syndrome is well established, but how menin loss/inactivation initiates tumorigenesis is not well understood. We show that menin activates the long noncoding RNA maternally expressed gene 3 (Meg3) by histone-H3 lysine-4 trimethylation and CpG hypomethylation at the Meg3 promoter CRE site, to allow binding of the transcription factor cAMP response element-binding protein. We found that Meg3 has tumor-suppressor activity in PNET cells because the overexpression of Meg3 in MIN6 cells (insulin-secreting mouse PNET cell line) blocked cell proliferation and delayed cell cycle progression. Gene expression microarray analysis showed that Meg3 overexpression in MIN6 mouse insulinoma cells down-regulated the expression of the protooncogene c-Met (hepatocyte growth factor receptor), and these cells showed significantly reduced cell migration/invasion. Compared with normal islets, mouse or human MEN1-associated PNETs expressed less MEG3 and more c-MET. Therefore, a tumor-suppressor long noncoding RNA (MEG3) and suppressed protooncogene (c-MET) combination could elicit menin's tumor-suppressor activity. Interestingly, MEG3 and c-MET expression was also altered in human sporadic insulinomas (insulin secreting PNETs) with hypermethylation at the MEG3 promoter CRE-site coinciding with reduced MEG3 expression. These data provide insights into the β-cell proliferation mechanisms that could retain their functional status. Furthermore, in MIN6 mouse insulinoma cells, DNA-demethylating drugs blocked cell proliferation and activated Meg3 expression. Our data suggest that the epigenetic activation of lncRNA MEG3 and/or inactivation of c-MET could be therapeutic for treating PNETs and insulinomas.

Indexed as

Epigenesis, GeneticGene Expression Regulation, NeoplasticAnimalsApoptosisCell CycleCell Line, TumorCell MovementCell ProliferationDNA MethylationHumansInsulinomaIslets of LangerhansMiceNeuroendocrine TumorsPancreatic NeoplasmsProto-Oncogene ProteinsMEG3 non-coding RNA, humanMEG3 non-coding RNA, mouseMen1 protein, mouseProto-Oncogene ProteinsProto-Oncogene Proteins c-metRNA, Long Noncoding

Identifiers

PMID25565142
PMCPMC4318878
OpenAlexW2115408721

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.