Knockdown of Skp2 by siRNA inhibits melanoma cell growth in vitro and in vivo

Journal of Dermatological Science
Yoshiyuki KatagiriShigeo Kondo

Abstract

Low levels of p27Kip1 expression are associated with poor prognosis in various malignancies including malignant melanoma. Recently, it has been reported that S phase kinase-interacting protein 2 (Skp2), the specific ubiquitin ligase subunit that targets p27Kip1 for degradation, was overexpressed and was inversely related to p27Kip1 levels in malignant melanoma with poor prognosis. We investigated whether small interfering RNA (siRNA)-mediated gene silencing of Skp2 can be employed in order to inhibit p27Kip1 down-regulation and suppress melanoma cell growth as a consequence in vitro and in vivo. We constructed a plasmid vector, which synthesizes siRNAs to determine the effects of decreasing the high constitutive levels of Skp2 protein in melanoma cells. Western blot and real-time RT-PCR were performed to examine the decreases of Skp2 protein and mRNA in vitro. Furthermore, melanoma cells were injected into the back of nude mice subcutaneously to examine the suppression of tumorigenicity targeting Skp2 gene silencing in vivo. Skp2 protein was decreased and the p27Kip1 protein was accumulated in Skp2 siRNA transfected melanoma cells. Skp2 siRNA inhibited the cell growth of melanoma cells in vitro. Moreover, Skp2 siRNA also suppre...Continue Reading

References

May 15, 1995·Genes & Development·C J Sherr, J M Roberts
Mar 9, 1995·Nature·D O Morgan
Jun 1, 1997·Nature Medicine·M MoriT Akiyoshi
Jan 13, 1998·Current Opinion in Cell Biology·A Hershko
Aug 26, 1998·The American Journal of Pathology·H KawanaT Kuriyama
Oct 29, 1998·The Journal of Biological Chemistry·K MoriH Ariga
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·S HatakeyamaK Nakayama
Nov 13, 1999·Nature Cell Biology·A C CarranoM Pagano
Nov 13, 1999·Nature Cell Biology·H SutterlütyW Krek
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·E LatresM Pagano
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·M GstaigerW Krek
Jul 11, 2002·The American Journal of Pathology·Sana YokoiJohji Inazawa
Jan 1, 2003·Seminars in Cancer Biology·Joanna Bloom, Michele Pagano
Jun 26, 2003·Cancer Science·Sana YokoiJohji Inazawa
Apr 23, 2004·The EMBO Journal·Masayoshi YadaKeiichi I Nakayama
Oct 20, 2004·Journal of Cutaneous Pathology·Qing LiJ Andrew Carlson
Jul 30, 2005·International Journal of Cancer. Journal International Du Cancer·Hidetoshi SumimotoYutaka Kawakami

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Citations

May 27, 2008·Nature Reviews. Cancer·David Frescas, Michele Pagano
Aug 22, 2008·Molecular Biology of the Cell·Rong Hu, Andrew E Aplin
Dec 6, 2008·Genes & Development·Gustavo A Miranda-CarboniTimothy F Lane
Oct 5, 2010·Pigment Cell & Melanoma Research·Amy E RoseIman Osman
Mar 26, 2013·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Chuan-Ming XieYi Sun
Jan 10, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sidi YangEmmanuel A Ho
Aug 24, 2006·Neoplasia : an International Journal for Oncology Research·Yi Sun
Apr 2, 2008·Biologicals : Journal of the International Association of Biological Standardization·Chao ShenCongyi Zheng
Jan 21, 2014·Journal of Cellular Physiology·Katerina D Fagan-SolisKathleen F Arcaro
Mar 8, 2013·Biochimica Et Biophysica Acta·Florian BassermannMichele Pagano
Apr 15, 2011·Molecular Oncology·Margaret RedpathAlan Spatz
Dec 25, 2012·Chemistry & Biology·Lily WuTimothy J Cardozo
Sep 23, 2006·Nature Reviews. Cancer·Daniela HoellerIvan Dikic
Jul 4, 2006·Nature Reviews. Drug Discovery·Grzegorz NalepaJ Wade Harper
Jan 18, 2008·European Journal of Immunology·Akiko NagasakaShinji Shimada
Jan 30, 2008·European Journal of Immunology·Silvia Bulfone-Paus, Ralf Paus
May 12, 2007·Expert Review of Anticancer Therapy·Ferdy J LejeuneDaniel Speiser
Jan 17, 2015·Oncoscience·Teruki YanagiShu-Ichi Matsuzawa
Aug 7, 2009·Acta Biochimica Et Biophysica Sinica·Jie XiaoJianhong Feng
May 26, 2017·Cancer Medicine·Jinyuan MaChunying Li
Feb 10, 2018·Oncotarget·Anna A BrożynaJ Andrew Carlson
Aug 11, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Guangdi ChenGang Li
Apr 4, 2021·Journal of Clinical Medicine·Frédéric SoysouvanhRobert Ballotti
Aug 28, 2021·International Journal of Molecular Sciences·Laura L ThompsonKirk J McManus

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