Improved Analysis of Prostate Cancer: VIM3, ATG7 and P53 Form a Complex and Activate miRNA 371a-3p.


Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Jun 2023
Historique:
received: 16 03 2023
revised: 31 03 2023
accepted: 05 04 2023
medline: 31 5 2023
pubmed: 30 5 2023
entrez: 29 5 2023
Statut: ppublish

Résumé

It is not possible to differentiate prostate carcinomas sufficiently to ensure that every patient receives the right therapy. New molecular markers are needed. Our objective was to identify a complex consisting of vimentin variant 3 (VIM3), autophagy-related protein 7 (ATG7) and tumor protein p53 (TP53) in prostate cancer cells and its effect on microRNA (miR)-371a-3p. Prostate cancer cell lines (PC3, DU145, LNCaP) and the benign prostatic hyperplasia cell line BPH-1 were cultured in growth medium for 24 h, then stimulated with endothelin 1 (EDN1) (50 nM) and withaferin A (2 nM) for 24 h. Cell extracts were then analyzed by western blot. The localization of VIM3, ATG7 and TP53 in the nucleus was demonstrated with immunofluorescence staining and complex formation was demonstrated by immunoprecipitation. Cancer cell migration was analyzed with a scratch assay and agarose drop analysis. The binding of the complex to the promoter of pri-miR-371a-3p was analyzed with a non-radioactive electrophoretic mobility shift assay. VIM3 knockdown using small interfering RNA and quantitative real-time polymerase chain reaction for miR-371a-3p were performed. The complex was present in the nucleus of prostate cancer cells and in the BPH-1 cell line. EDN1 increased the levels of the complex partners and cell migration, whereas withaferin A reduced the levels of the complex partners and migration. The complex bound to the promoter of pri-miR-371a-3p and might be involved in its transcription. Transfection with miR-371a-3p increased migration of prostate cancer cells. VIM3 knockdown reduced miR-371a-3p expression. The VIM3-ATG7-P53 complex, with its stimulatory effect on miR-371a-3p, may have the potential to be a marker for improved differentiation between prostate carcinomas, allowing tailored therapy.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
It is not possible to differentiate prostate carcinomas sufficiently to ensure that every patient receives the right therapy. New molecular markers are needed. Our objective was to identify a complex consisting of vimentin variant 3 (VIM3), autophagy-related protein 7 (ATG7) and tumor protein p53 (TP53) in prostate cancer cells and its effect on microRNA (miR)-371a-3p.
MATERIALS AND METHODS METHODS
Prostate cancer cell lines (PC3, DU145, LNCaP) and the benign prostatic hyperplasia cell line BPH-1 were cultured in growth medium for 24 h, then stimulated with endothelin 1 (EDN1) (50 nM) and withaferin A (2 nM) for 24 h. Cell extracts were then analyzed by western blot. The localization of VIM3, ATG7 and TP53 in the nucleus was demonstrated with immunofluorescence staining and complex formation was demonstrated by immunoprecipitation. Cancer cell migration was analyzed with a scratch assay and agarose drop analysis. The binding of the complex to the promoter of pri-miR-371a-3p was analyzed with a non-radioactive electrophoretic mobility shift assay. VIM3 knockdown using small interfering RNA and quantitative real-time polymerase chain reaction for miR-371a-3p were performed.
RESULTS RESULTS
The complex was present in the nucleus of prostate cancer cells and in the BPH-1 cell line. EDN1 increased the levels of the complex partners and cell migration, whereas withaferin A reduced the levels of the complex partners and migration. The complex bound to the promoter of pri-miR-371a-3p and might be involved in its transcription. Transfection with miR-371a-3p increased migration of prostate cancer cells. VIM3 knockdown reduced miR-371a-3p expression.
CONCLUSION CONCLUSIONS
The VIM3-ATG7-P53 complex, with its stimulatory effect on miR-371a-3p, may have the potential to be a marker for improved differentiation between prostate carcinomas, allowing tailored therapy.

Identifiants

pubmed: 37247912
pii: 43/6/2407
doi: 10.21873/anticanres.16408
doi:

Substances chimiques

ATG7 protein, human EC 6.2.1.45
Autophagy-Related Protein 7 EC 6.2.1.45
MicroRNAs 0
Tumor Suppressor Protein p53 0
TP53 protein, human 0
Vimentin 0
MIRN371 microRNA, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2407-2416

Informations de copyright

Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Elena K Nohl (EK)

Department of Urology, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany; enohl@smail.uni-koeln.de.

Jasmin Behring (J)

Department of Urology, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.

Ersen Kameri (E)

Department of Urology, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.

Barbara Köditz (B)

Department of Urology, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.

Tim Nestler (T)

Department of Urology, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.

Axel Heidenreich (A)

Department of Urology, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
Department of Urology, Medical University, Vienna, Austria.

Melanie VON Brandenstein (M)

Department of Urology, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.

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Classifications MeSH