Evidence map›Paper›PMID 34262023›Full record

ArticleCell death & disease2021

The long noncoding RNA HOTAIRM1 controlled by AML1 enhances glucocorticoid resistance by activating RHOA/ROCK1 pathway through suppressing ARHGAP18.

Liang Liang, Wenbin Gu, Meng Li, Ran Gao, Xin Zhang, Chongye Guo, Shuangli Mi

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 25% 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

14 citing papers in PubMed, 17 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

7 authors at 2 institutions in 1 country.

Liang LiangKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China.
Wenbin GuKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China.
Meng LiKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China.
Ran GaoKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China.
Xin ZhangKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China.
Chongye GuoKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China.
Shuangli MiKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China. mishl@big.ac.cn.ORCID 0000-0001-8883-3215
Chinese Academy of Sciences · CNBeijing Institute of Genomics · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acquired resistance to glucocorticoids (GCs) is an obstacle to the effective treatment of leukemia, but the molecular mechanisms of steroid insensitivity have not been fully elucidated. In this study, we established an acquired GC-resistant leukemia cell model and found a long noncoding RNA, HOTAIRM1, was overexpressed in the resistant cells by transcriptional profiling, and was higher expressed in patients with poor prognosis. The whole-genome-binding sites of HOTAIRM1 were determined by ChIRP-seq (chromatin isolation by RNA purification combined with sequencing) analysis. Further study determined that HOTAIRM1 bound to the transcriptional inhibitory region of ARHGAP18 and repressed the expression of ARHGAP18, which led to the increase of RHOA/ROCK1 signaling pathway and promoted GC resistance through antiapoptosis of leukemia cells. The inhibition of ROCK1 in GC-resistant cells could restore GCs responsiveness. In addition, HOTAIRM1 could also act as a protein sequester to prevent transcription factor AML1(acute myeloid leukemia 1) from binding to the regulatory region of ARHGAP18 by interacting with AML1. At last, we also proved AML1 could directly activate the expression of HOTAIRM1 through binding to the promoter of HOTAIRM1, which enriched the knowledge on the regulation of lncRNAs. This study revealed epigenetic causes of glucocorticoid resistance from the perspective of lncRNA, and laid a foundation for the optimization of glucocorticoid-based leukemia treatment strategy in clinic.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsApoptosisBinding SitesCell Line, TumorCore Binding Factor Alpha 2 SubunitDexamethasoneGene Expression Regulation, LeukemicGlucocorticoidsGTPase-Activating ProteinsHEK293 CellsHumansLeukemiaMicroRNAsProtein BindingrhoA GTP-Binding ProteinAntineoplastic AgentsARHGAP18 protein, humanCore Binding Factor Alpha 2 SubunitDexamethasoneGlucocorticoidsGTPase-Activating Proteinslong non-coding RNA HOTAIRM1, humanMicroRNAsrhoA GTP-Binding ProteinRHOA protein, humanrho-Associated KinasesROCK1 protein, humanRUNX1 protein, human

Identifiers

PMID34262023
PMCPMC8280127
OpenAlexW3178759443

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.