Evidence map›Paper›PMID 29983868›Full record

ArticleOncotarget2018

MiR-199a-3p decreases esophageal cancer cell proliferation by targeting p21 activated kinase 4.

Pornima Phatak, Whitney M Burrows, Ingrid E Chesnick, Mohan E Tulapurkar, Jaladanki N Rao, Douglas J Turner, Anne W Hamburger, Jian-Ying Wang, James M Donahue

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 21% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

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

9 authors at 2 institutions in 1 country.

Pornima PhatakDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Whitney M BurrowsDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ingrid E ChesnickBaltimore Veterans Affairs Medical Center, Baltimore, MD 21201, USA.
Mohan E TulapurkarDivision of Pulmonary and Critical Care, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Jaladanki N RaoDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Douglas J TurnerDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Anne W HamburgerDepartment of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Jian-Ying WangDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
James M DonahueDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
University of Maryland, Baltimore · USVeterans Health Administration · US

Funding

Intestinal Mucosal Growth in Health & Surgical DiseasesR01DK057819 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI Jian-Ying Wang · 2000 to 2026
$7.4M
Surgical Studies of Gut PermeabilityR01DK068491 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI Jian-Ying Wang · 2004 to 2026
$7.0M
Barrier Dysfunction in Severe Surgical DiseasesI01BX000113 · VA · BALTIMORE VA MEDICAL CENTER · PI TURNER, DOUGLAS J · 2009 to 2024
–
SURGICAL STUDIES ON MUCOSAL HOMEOSTASISI01BX000713 · VA · BALTIMORE VA MEDICAL CENTER · PI WANG, JIAN-YING · 2011 to 2024
–
BLRD VA I01 BX000113BLRD VA I01 BX000713CSRD VA I01 CX001434NIDDK NIH HHS R01 DK057819
6 · The paper itself

Abstract

Although microRNA (miR) 199a-3p functions as a tumor suppressor in multiple malignancies, its expression and role in esophageal cancer have not been studied. Based on our previous observation that miR-199a-3p is markedly downregulated in esophageal cancer cell lines relative to esophageal epithelial cells, we examined the function of miR-199a-3p in these cells. MiR-199a-3p is predicted to bind with high affinity to the mRNA of p21 activated kinase 4 (PAK4). This kinase has been shown to be overexpressed in several malignancies and to modulate proliferation and motility. The current study is designed to determine whether miR-199a-3p regulates the expression of PAK4 in esophageal cancer cells and to understand the functional consequences of this interaction. Herein, we demonstrate reduced expression of miR-199a-3p in human esophageal cancer specimens and cell lines compared to esophageal epithelial cells, with associated increased expression of PAK4. Forced expression of miR-199a-3p decreases expression of PAK4 in esophageal cancer cell lines. Mechanistic studies reveal that miR-199a-3p binds to the 3'UTR of PAK4 mRNA. This interaction results in reduced levels of PAK4 mRNA due to decreased mRNA stability. Downregulation of PAK4 leads to decreased cyclin D1 (CD1) transcription and protein expression, resulting in markedly impaired cellular proliferation. When PAK4 expression is rescued, both CD1 transcription and protein return to baseline levels. Our results show that miR-199a-3p functions as a tumor suppressor in esophageal cancer cells through repression of PAK4. These findings suggest that both miR-199a-3p and PAK4 may be novel therapeutic targets in the treatment of esophageal cancer.

Indexed as

esophageal cancermicroRNAmiR-199a-3pPAK4

Identifiers

PMID29983868
PMCPMC6033339
OpenAlexW2808827801

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.