Evidence map›Paper›PMID 21963845›Full record

ArticleOncogene2012

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes.

T Schepeler, A Holm, P Halvey, I Nordentoft, P Lamy, E M Riising, L L Christensen, K Thorsen, D C Liebler, K Helin and 2 more

Open access · bronzeAbstract readComparative Study
PubMed Publisher
In one paragraph

Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

38 citing papers in PubMed, 72 citations in OpenAlex.

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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

12 authors at 3 institutions in 2 countries.

T SchepelerDepartment of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus N, Denmark.
A Holm
P Halvey
I Nordentoft
P Lamy
E M Riising
L L Christensen
K Thorsen
D C Liebler
K Helin
T F Ørntoft
C L Andersen
Aarhus University Hospital · DKUniversity of Copenhagen · DKVanderbilt University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant activation of the Wnt signaling pathway is causally involved in the formation of most colorectal cancers (CRCs). Although detailed knowledge exists regarding Wnt-regulated protein-coding genes, much less is known about the possible involvement of non-coding RNAs. Here we used TaqMan Array MicroRNA Cards, capable of detecting 664 unique human microRNAs (miRNAs), to describe changes of the miRNA transcriptome following disruption of beta-catenin/TCF4 activity in DLD1 CRC cells. Most miRNAs appeared to respond independent of host gene regulation and proximal TCF4 chromatin occupancy as inferred from expression microarray and ChIP-chip data. A module of miRNAs induced by abrogated Wnt signaling in vitro was downregulated in two independent series of human primary CRCs (n=76) relative to normal adjacent mucosa (n=34). Several of these miRNAs (miR-145, miR-126, miR-30e-3p and miR-139-5p) markedly inhibited CRC cell growth in vitro when ectopically expressed. By using an integrative approach of proteomics and expression microarrays, we found numerous mRNAs and proteins to be affected by ectopic miR-30e-3p levels. This included HELZ and PIK3C2A that were directly repressed by several miRNA binding sites as confirmed by luciferase reporter assays in combination with mutational analyses. Finally, small interfering RNA-mediated downregulation of PIK3C2A, but not HELZ, was sufficient on its own to restrict CRC cell growth. Collectively, our study demonstrates that multiple miRNAs are upregulated as a consequence of forced attenuation of Wnt signaling in CRC cells, and some of these miRNAs inhibit cell growth with concomitant suppression of several growth-stimulatory cancer-related genes.

Indexed as

TranscriptomeAgedAged, 80 and overBasic Helix-Loop-Helix Leucine Zipper Transcription Factorsbeta CateninCell Line, TumorCell ProliferationChromatography, LiquidColonColorectal NeoplasmsFemaleGene Expression ProfilingGenes, DominantHumansLuciferasesMaleBasic Helix-Loop-Helix Leucine Zipper Transcription Factorsbeta CateninLuciferasesMicroRNAsRNA, MessengerRNA, Small InterferingTCF4 protein, humanTranscription Factor 4Transcription Factors

Identifiers

PMID21963845
OpenAlexW1968627845

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.