miR-221-3p Regulates VEGFR2 Expression in High-Risk Prostate Cancer and Represents an Escape Mechanism from Sunitinib In Vitro

Journal of Clinical Medicine
Markus KrebsBurkhard Kneitz

Abstract

Downregulation of miR-221-3p expression in prostate cancer (PCa) predicted overall and cancer-specific survival of high-risk PCa patients. Apart from PCa, miR-221-3p expression levels predicted a response to tyrosine kinase inhibitors (TKI) in clear cell renal cell carcinoma (ccRCC) patients. Since this role of miR-221-3p was explained with a specific targeting of VEGFR2, we examined whether miR-221-3p regulated VEGFR2 in PCa. First, we confirmed VEGFR2/KDR as a target gene of miR-221-3p in PCa cells by applying Luciferase reporter assays and Western blotting experiments. Although VEGFR2 was mainly downregulated in the PCa cohort of the TCGA (The Cancer Genome Atlas) database, VEGFR2 was upregulated in our high-risk PCa cohort (n = 142) and predicted clinical progression. In vitro miR-221-3p acted as an escape mechanism from TKI in PC3 cells, as displayed by proliferation and apoptosis assays. Moreover, we confirmed that Sunitinib induced an interferon-related gene signature in PC3 cells by analyzing external microarray data and by demonstrating a significant upregulation of miR-221-3p/miR-222-3p after Sunitinib exposure. Our findings bear a clinical perspective for high-risk PCa patients with low miR-221-3p levels since this c...Continue Reading

References

Jul 30, 2003·The Journal of Biological Chemistry·Sarmishtha DeTatiana V Byzova
Apr 19, 2005·Cancer Research·Gavin P DunnRobert D Schreiber
Dec 11, 2007·Trends in Pharmacological Sciences·Angelika KuehbacherStefanie Dimmeler
Oct 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·James H FinkeRonald Bukowski
Mar 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jennifer S KoJames H Finke
May 1, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M Dror MichaelsonM R Smith
Jul 9, 2009·International Journal of Cancer. Journal International Du Cancer·Martin SpahnBurkhard Kneitz
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Apr 17, 2013·BMC Bioinformatics·Edward Y ChenAvi Ma'ayan
Jul 24, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Heba W Z KhellaGeorge M Yousef
Aug 13, 2015·ELife·Vikram AgarwalDavid P Bartel
May 5, 2016·Nucleic Acids Research·Maxim V KuleshovAvi Ma'ayan
Oct 5, 2016·JCI Insight·Jesús García-DonasCristina Rodriguez-Antona
Jan 18, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francesca FornariLaura Gramantieri
Jul 22, 2017·Neoplasia : an International Journal for Oncology Research·Darshan S ChandrashekarSooryanarayana Varambally
Nov 18, 2017·Nucleic Acids Research·Antonio FabregatPeter D'Eustachio
Feb 9, 2018·Bioinformatics·Zichen WangAvi Ma'ayan
May 8, 2019·Proceedings of the National Academy of Sciences of the United States of America·Wassim AbidaCharles L Sawyers
Jun 4, 2019·International Journal of Molecular Sciences·Zsombor Melegh, Sebastian Oltean
Nov 24, 2019·Journal of Clinical Medicine·Patrizia LeoneVito Racanelli
Jan 8, 2020·Journal of Clinical Medicine·Raluca Ioana TeleanuDaniel Mihai Teleanu

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Citations

Jul 16, 2020·Cancers·Antonio Giovanni SolimandoDomenico Ribatti
May 28, 2020·Journal of Clinical Medicine·Antonella ArgentieroNicola Silvestris
Oct 13, 2020·Frontiers in Cell and Developmental Biology·Dominik A BarthMartin Pichler
Jul 3, 2021·Biomedicines·Luis Javier Martínez-GonzálezMaría Jesus Alvarez-Cubero
Oct 12, 2021·Experimental and Therapeutic Medicine·Yuan GuChaozhao Liang
Nov 2, 2021·Frontiers in Oncology·Yangzhou LiuZhigang Zhao

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Methods Mentioned

BETA
transfection
PCRs
transfections
Assay

Software Mentioned

Reactome 2016
Reactome
R
Targetscan
UALCAN
Enrichr
L1000
L1000 Fireworks Display

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