Evidence map›Paper›PMID 30773595›Full record

ArticleNucleic acids research2019

LncRNA PCAT1 activates AKT and NF-κB signaling in castration-resistant prostate cancer by regulating the PHLPP/FKBP51/IKKα complex.

Zhiqun Shang, Jianpeng Yu, Libin Sun, Jing Tian, Shimiao Zhu, Boya Zhang, Qian Dong, Ning Jiang, Amilcar Flores-Morales, Chawnshang Chang and 1 more

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

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 2 pooled it
9.6field-weighted citation impact, top 1% 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

110 citing papers in PubMed, 2 syntheses or guidelines pooled it, 211 citations in OpenAlex.

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50 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 3 countries.

Zhiqun ShangTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Jianpeng YuTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Libin SunTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Jing TianTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Shimiao ZhuTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Boya ZhangTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Qian DongTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Ning JiangTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Amilcar Flores-MoralesDepartment of Health Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Chawnshang ChangTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Yuanjie NiuTianjin Institute of Urology, the 2nd Hospital of Tianjin Medical University, Tianjin 300211, China.
Second Hospital of Tianjin Medical University · CNShanxi Medical University · CNUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In PTEN-deficient prostate cancers, AKT signaling may be activated upon suppression of androgen receptor signaling. Activation of AKT as well as NF-κB signaling involves a key regulatory protein complex containing PHLPP, FKBP51 and IKKα. Here, we report a critical role of lncRNA PCAT1 in regulating the PHLPP/FKBP51/IKKα complex and progression of castration-resistant prostate cancer (CRPC). Using database queries, bioinformatic analyses, as well as RIP and RNA pull-down assays, we discovered and validated that the lncRNA-PCAT1 perturbs the PHLPP/FKBP51/IKKα complex and activates AKT and NF-κB signaling. Expression of lncRNA-PCAT1 is positively linked to CRPC progression. PCAT1 binds directly to FKBP51, displacing PHLPP from the PHLPP/FKBP51/IKKα complex, leading to activation of AKT and NF-κB signaling. Targeting PCAT1 restores PHLPP binding to FKBP1 leading to suppression of AKT signaling. Preclinical study in a mouse model of CRPC suggests therapeutic potential by targeting lncRNA PCAT1 to suppress CRPC progression. Together, the newly identified PCAT1/FKBP51/IKKα complex provides mechanistic insight in the interplay between AKT, NF-κB and AR signaling in CRPC, and the preclinical studies suggest that a novel role for PCAT1 as a therapeutic target.

Indexed as

Gene Expression Regulation, NeoplasticAdenocarcinomaAnimalsCell Line, TumorCell ProliferationDatasets as TopicHumansI-kappa B KinaseMaleMiceMice, NudeNF-kappa BNuclear ProteinsPhosphoprotein PhosphatasesProstateProstatic Neoplasms, Castration-ResistantCHUK protein, humanI-kappa B Kinaselong non-coding RNA PCAT1, humanNF-kappa BNuclear ProteinsPHLPP1 protein, humanPhosphoprotein PhosphatasesProto-Oncogene Proteins c-aktRNA, Long NoncodingRNA, Small InterferingTacrolimus Binding Protein 5Tacrolimus Binding Proteins

Identifiers

PMID30773595
PMCPMC6486551
OpenAlexW2915362329

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.