Evidence mapPaperPMID 40436833Full record

ArticleCell death & disease2025

miR-181a-5p mediates the effects of BMP4 on intestinal cell proliferation and differentiation.

Chang Li, Yuning Zhou, Zhijie Yin, Yinping Jiang, Jinpeng Liu, Heidi L Weiss, Qingding Wang, B Mark Evers

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

8 authors.

Chang Li *Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
Yuning Zhou *Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
Zhijie YinMarkey Cancer Center, University of Kentucky, Lexington, KY, USA.
Yinping JiangMarkey Cancer Center, University of Kentucky, Lexington, KY, USA.
Jinpeng LiuMarkey Cancer Center, University of Kentucky, Lexington, KY, USA.
Heidi L WeissMarkey Cancer Center, University of Kentucky, Lexington, KY, USA.
Qingding WangMarkey Cancer Center, University of Kentucky, Lexington, KY, USA. qingding.wang@uky.edu.ORCID http://orcid.org/0009-0002-4797-4876
B Mark EversMarkey Cancer Center, University of Kentucky, Lexington, KY, USA. mark.evers@uky.edu.ORCID http://orcid.org/0000-0002-9425-2342

Funding

University of Kentucky Markey Cancer Center – Cancer Center Support GrantP30CA177558 · UNIVERSITY OF KENTUCKY · 2025 to 2025
$2.8M
SURGICAL STUDIES OF FUNCTIONAL GENE EXPRESSIONR01DK048498 · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · 1996 to 2005
$1.8M
Targeting the Immunosuppressive Tumor Microenvironment for Colorectal Cancer TreatmentR01CA272669 · UNIVERSITY OF KENTUCKY · 2025 to 2025
$400k
NCI NIH HHS P30 CA177558NCI NIH HHS R01 CA272669NIDDK NIH HHS R01 DK048498
6 · The paper itself

Abstract

The intestinal mucosa undergoes a dynamic process of continual proliferation, differentiation, and apoptosis. Delineating the mechanisms involved in intestinal epithelial cell (IEC) differentiation is crucial to our understanding of not only normal gut adaptation but also aberrant intestinal growth. Bone morphogenetic protein (BMP) signaling is a pivotal regulator of intestinal proliferation and differentiation. However, the molecular underpinnings of the BMP pathway in this context are not entirely known. Here, we show a key role for the BMP4/microRNA (miR)-181/glycolysis signaling pathway in the maintenance of intestinal epithelial cell proliferation and differentiation. Treatment with BMP4 increased the expression of enterocyte markers and decreased proliferation of IECs, and importantly, decreased the expression of miR-181a-5p in mouse and human intestinal organoids. miR-181a-5p is a member of the miR-181 family with the highest expression in IECs. Treatment with locked nucleic acid (LNA) miR-181a-5p inhibitor significantly increased enterocyte differentiation as noted by increased expression of enterocyte markers in human and mouse intestinal organoids. In addition, LNA miR-181a-5p inhibitor repressed intestinal stem cell self-renewal as noted by the decreased organoid forming efficiency and expression of Ki67, cyclin D1, OLFM4 in human and mouse intestinal organoids. Moreover, in vivo administration of LNA miR-181a-5p inhibitor enhanced increased intestinal enterocyte differentiation and repressed intestinal cell proliferation. In contrast, overexpression of miR-181a-5p mimic decreased basal and BMP4-induced expression of enterocyte markers. Moreover, BMP4 treatment or inhibition of miR-181a-5p repressed hexokinase (HK) 1 expression and inhibited glycolysis. Consistently, knockdown of HK1 or inhibition of glycolysis using 2-deoxyglucose (2-DG) promoted enterocyte maturation and inhibited proliferation of IECs. Together, we provide evidence showing that miR-181a-5p inhibits intestinal enterocyte differentiation and promotes IEC proliferation through HK1-dependent glycolysis. Importantly, our findings identify miR-181a-5p as downstream in mediating BMP4 induction of enterocyte differentiation and inhibition of proliferation in IECs.

Indexed as

Bone Morphogenetic Protein 4Cell DifferentiationIntestinal MucosaMicroRNAsAnimalsCell ProliferationEnterocytesHumansMiceOrganoidsSignal TransductionBMP4 protein, humanBone Morphogenetic Protein 4MicroRNAsMIrn181 microRNA, humanmirn181 microRNA, mouse

Identifiers

PMID40436833
PMCPMC12120108

What Socratic 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 Socratic graph.