Targeted Knockdown of the Kinetochore Protein D40/Knl-1 Inhibits Human Cancer in a p53 Status-Independent Manner

Scientific Reports
Yuri N UrataMasato Takimoto

Abstract

The D40 gene encodes a kinetochore protein that plays an essential role in kinetochore formation during mitosis. Short inhibitory RNA against D40, D40 siRNA, has been shown to deplete the D40 protein in the human cancer cell line HeLa, which harbors wild-type p53, and this activity was followed by the significant inhibition of cell growth and induction of apoptotic cell death. The p53-null cancer cell line, PC-3M-luc, is also sensitive to the significant growth inhibition and cell death induced by D40 siRNA. The growth of PC-3M-luc tumors transplanted into nude mice was inhibited by the systemic administration of D40 siRNA and the atelocollagen complex. Furthermore, D40 siRNA significantly inhibited growth and induced apoptotic cell death in a cell line with a gain-of-function (GOF) mutation in p53, MDA-MB231-luc, and also inhibited the growth of tumors transplanted into mice when administered as a D40 siRNA/atelocollagen complex. These results indicated that D40 siRNA induced apoptotic cell death in human cancer cell lines, and inhibited their growth in vitro and in vivo regardless of p53 status. Therefore, D40 siRNA is a potential candidate anti-cancer reagent.

References

Jul 2, 1992·Nature·D P Lane
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·S KamadaY Tsujimoto
Apr 26, 2000·Nucleic Acids Symposium Series·G WeiN Kuzumaki
Dec 1, 2000·Nature·B VogelsteinA J Levine
Jun 28, 2002·British Journal of Cancer·M TakimotoN Kuzumaki
Dec 8, 2004·Reproduction : the Official Journal of the Society for the Study of Fertility·Takumi SasaoMasato Takimoto
Jul 22, 2005·Nature Reviews. Cancer·Andrew J G SimpsonLloyd J Old
Aug 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Fumitaka TakeshitaTakahiro Ochiya
Dec 6, 2006·Annals of the New York Academy of Sciences·Koji HanaiTakahiro Ochiya
Jul 11, 2007·The Journal of Cell Biology·Yohei NiikuraKatsumi Kitagawa
Apr 17, 2008·Cell Cycle·Katsumi Kitagawa, Yohei Niikura
Apr 7, 2009·Cell·Maddalena AdornoStefano Piccolo
May 19, 2009·Nature Cell Biology·Shu-Ping WangPan-Chyr Yang
Aug 21, 2009·Nature Reviews. Cancer·Ran Brosh, Varda Rotter
Sep 10, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Fumitaka TakeshitaTakahiro Ochiya
Sep 18, 2009·Nature Reviews. Cancer·Karen H Vousden, Kevin M Ryan
Sep 25, 2009·Nature Reviews. Cancer·Arnold J Levine, Moshe Oren
Oct 24, 2009·Trends in Genetics : TIG·Gemma K Thornton, C Geoffrey Woods
Jan 13, 2010·Cell·Patricia A J MullerKaren H Vousden
Jul 7, 2010·Cell·Graziano MartelloStefano Piccolo
Nov 30, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Kevin M Ryan
Jun 11, 2011·Journal of Cellular Physiology·Takashi AsaiStephen D Nimer
Nov 10, 2011·Cancer Research·Shyhmin HuangPaul M Harari
Feb 15, 2012·The Journal of Cell Biology·Julien EspeutArshad Desai
Aug 18, 2012·Nature Reviews. Cancer·Heiko Hermeking
Sep 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Paola TucciGerry Melino
Sep 18, 2012·Human Molecular Genetics·Anne GeninMarc Abramowicz
Dec 25, 2012·Nature Cell Biology·Patricia A J Muller, Karen H Vousden
Feb 19, 2013·Oncogene·A RufiniG Melino
Dec 7, 2013·Chromosoma·Gina V Caldas, Jennifer G DeLuca
Mar 22, 2014·Cancer Cell·Patricia A J Muller, Karen H Vousden
Mar 26, 2014·The Journal of Cell Biology·Shota YamauchiKeiko Kawauchi

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Citations

Jun 16, 2017·Endocrine-related Cancer·Shivangi Agarwal, Dileep Varma
Mar 4, 2020·International Journal of Molecular Sciences·Xiaokun ZhouDan Xu
Apr 14, 2020·Cell Biochemistry and Function·Yuanbo CuiFangxia Guan
Jul 19, 2019·Technology in Cancer Research & Treatment·Tianliang BaiBinghui Li
Sep 14, 2017·Congenital Anomalies·Masato Takimoto

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Methods Mentioned

BETA
transfection
ELISA

Software Mentioned

Image Gauge
Cell Quest

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