Evidence map›Paper›PMID 33005248›Full record

ArticleExperimental and therapeutic medicine2020

GSK-3β mediates the effects of HNF-1β overexpression in ovarian clear cell carcinoma.

Naoki Kawahara, Ayano Mizutani, Sho Matsubara, Yoshinori Takeda, Hiroshi Kobayashi

Abstract read
In one paragraph

Article in Experimental and therapeutic medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

5 authors.

Naoki KawaharaDepartment of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Ayano MizutaniDepartment of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Sho MatsubaraDepartment of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Yoshinori TakedaDepartment of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Hiroshi KobayashiDepartment of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara 634-8522, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deubiquitinase USP28 is a target gene of the transcription factor HNF1 homeobox β (HNF-1β), which promotes the survival of ovarian clear cell carcinoma (OCCC) cell lines. However, the pharmacological inhibition of HNF-1β can cause several adverse effects as it is abundantly expressed in numerous organ systems, including the kidney, liver, pancreas and digestive tract. Therefore, small interfering RNA (siRNA) screening was performed in the current study to identify other potential downstream targets of the HNF-1β-mediated pathway. The results revealed that glycogen synthase kinase-3β (GSK-3β) may be a potential downstream target affecting cell viability. To further clarify the effects of GSK-3β, two human OCCC cell lines, TOV-21G (HNF-1β overexpressing line) and ES2 (HNF-1β negative) were transfected with siRNA targeting GSK-3β or control vectors. Loss-of-function studies using RNAi-mediated gene silencing indicated that HNF-1β facilitated GSK-3β expression, resulting in the loss of phosphorylated nuclear factor-κB (p-NFκB) and the reduction of TOV-21G cell proliferation. The cell proliferation assay also revealed that GSK-3β inhibitors rescued the effects of HNF-1β silencing on cell viability in a dose-dependent manner. Furthermore, the GSK-3β inhibitor, AR-A014418, effectively inhibited tumor cell proliferation in a xenograft mouse model. In conclusion and to the best of our knowledge, the current study was the first to determine that GSK-3β is a target gene of HNF-1β. In addition, the results of the present study revealed the novel HNF-1β-GSK-3β-p-NFκB pathway, occurring in response to DNA damage. Targeting this pathway may therefore represent a putative, novel, anticancer strategy in patients with OCCC.

Indexed as

glycogen synthase kinase-3βhepatocyte nuclear factor-1βnuclear factor-κBovarian clear cell carcinoma

Identifiers

PMID33005248
PMCPMC7523276

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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.