Evidence map›Paper›PMID 26930719›Full record

ArticleOncotarget2016

Cis-acting elements in its 3' UTR mediate post-transcriptional regulation of KRAS.

Minlee Kim, Nicole Kogan, Frank J Slack

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 27% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. The Nefarious Nexus of Noncoding RNAs in Cancer.International journal of molecular sciences · 2018
    Review
  8. Article
  9. Non-coding RNA networks in cancer.Nature reviews. Cancer · 2018
    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

3 authors at 2 institutions in 1 country.

Minlee KimDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Nicole KoganDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Frank J SlackInstitute for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
Beth Israel Deaconess Medical Center · USMassachusetts Institute of Technology · US

Funding

MicroRNAs to Understand Cause and Outcome in Breast CancerR01CA157749 · NCI · YALE UNIVERSITY · PI SLACK, FRANK J., WEIDHAAS, JOANNE B · 2012 to 2016
$1.7M
NCI NIH HHS R01 CA157749
6 · The paper itself

Abstract

Multiple RNA-binding proteins and non-coding RNAs, such as microRNAs (miRNAs), are involved in post-transcriptional gene regulation through recognition motifs in the 3' untranslated region (UTR) of their target genes. The KRAS gene encodes a key signaling protein, and its messenger RNA (mRNA) contains an exceptionally long 3' UTR; this suggests that it may be subject to a highly complex set of regulatory processes. However, 3' UTR-dependent regulation of KRAS expression has not been explored in detail. Using extensive deletion and mutational analyses combined with luciferase reporter assays, we have identified inhibitory and stabilizing cis-acting regions within the KRAS 3' UTR that may interact with miRNAs and RNA-binding proteins, such as HuR. Particularly, we have identified an AU-rich 49-nt fragment in the KRAS 3' UTR that is required for KRAS 3' UTR reporter repression. This element contains a miR-185 complementary element, and we show that overexpression of miR-185 represses endogenous KRAS mRNA and protein in vitro. In addition, we have identified another 49-nt fragment that is required to promote KRAS 3' UTR reporter expression. These findings indicate that multiple cis-regulatory motifs in the 3' UTR of KRAS finely modulate its expression, and sequence alterations within a binding motif may disrupt the precise functions of trans-regulatory factors, potentially leading to aberrant KRAS expression.

Indexed as

Gene Expression Regulation, NeoplasticRegulatory Sequences, Nucleic Acid3' Untranslated RegionsBase SequenceGenes, ReporterHumansNeoplasmsPromoter Regions, GeneticProto-Oncogene Proteins p21(ras)RNA Processing, Post-TranscriptionalTumor Cells, Cultured3' Untranslated RegionsKRAS protein, humanProto-Oncogene Proteins p21(ras)3′ UTRKRASmicroRNAs (miRNAs)miR-185post-transcriptional regulation

Identifiers

PMID26930719
PMCPMC4914247
OpenAlexW2290936399

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.