Evidence map›Paper›PMID 41981249›Full record

ArticleCommunications biology2026

Allosteric inhibition of RAN decreases miR-126 biogenesis in endothelial cells and controls acute myeloid leukemia growth.

Melissa Valerio, Wenyuan Wei, Hyunjun Kang, Ning Ma, Supriyo Bhattacharya, Genevieve Baker, Weidong Hu, Lianjun Zhang, Dinh Hoa Hoang, Jia Feng and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Melissa Valerio *Department of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA.
Wenyuan Wei *Irell and Manella Graduate School of Biosciences, City of Hope, Duarte, CA, USA.
Hyunjun KangDepartment of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA.
Ning MaDepartment of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0000-0003-4653-7797
Supriyo BhattacharyaDepartment of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0000-0003-0483-2149
Genevieve BakerDepartment of Molecular Diagnostics & Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Weidong HuBeckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0003-3911-5262
Lianjun ZhangDepartment of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-5285-0088
Dinh Hoa HoangDepartment of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA.
Jia FengDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, China.ORCID http://orcid.org/0000-0001-9968-2360
Hongyu ZhangDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, China.
Bin ZhangDepartment of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0003-4703-7524
J Jefferson P PerryDepartment of Molecular Diagnostics & Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0000-0001-9889-3502
Nagarajan VaidehiDepartment of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA. nvaidehi@coh.org.ORCID http://orcid.org/0000-0001-8100-8132
Le Xuan Truong NguyenDepartment of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA. lenguyen@coh.org.ORCID http://orcid.org/0000-0001-5464-0861
Guido MarcucciDepartment of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA. gmarcucci@coh.org.ORCID http://orcid.org/0000-0002-3983-5908

Funding

U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1R01CA205247U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30CA33572
6 · The paper itself

Abstract

The small GTPase RAN plays a role in the biogenesis of mature miR-126, which is supplied by the bone marrow arterioles to leukemic stem cells (LSCs). MiR-126 supports the homeostasis of LSCs that initiate and maintain acute myeloid leukemia (AML). While therapeutic targeting of RAN has been difficult due to its structural features, through molecular dynamics simulations and docking studies, we have identified MAR-3.6.2 as a novel allosteric inhibitor that binds in a cryptic pocket in the C-terminal domain of RAN. We showed that MAR-3.6.2 disrupted RAN interaction with its guanine nucleotide exchange factor RCC1 and prevented the nuclear switch of RAN-GDP to RAN-GTP. This in turn led to RAN nuclear retention and reduced the RAN/XPO5-mediated export of pre-miR-126, thereby limiting mature miR-126 biogenesis in endothelial cells and their exogenous supply of mature miR-126 to LSCs. In a Mll

Indexed as

Endothelial CellsLeukemia, Myeloid, AcuteMicroRNAsran GTP-Binding ProteinAllosteric RegulationAnimalsHumansMiceMicroRNAsMIRN126 microRNA, humanran GTP-Binding ProteinRAN protein, human

Identifiers

PMID41981249
PMCPMC13254346

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.