論文

査読有り 国際誌
2018年6月11日

An anionic phthalocyanine decreases NRAS expression by breaking down its RNA G-quadruplex.

Nature communications
  • Keiko Kawauchi
  • Wataru Sugimoto
  • Takatoshi Yasui
  • Kohei Murata
  • Katsuhiko Itoh
  • Kazuki Takagi
  • Takaaki Tsuruoka
  • Kensuke Akamatsu
  • Hisae Tateishi-Karimata
  • Naoki Sugimoto
  • Daisuke Miyoshi
  • 全て表示

9
1
開始ページ
2271
終了ページ
2271
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41467-018-04771-y

Aberrant activation of RAS signalling pathways contributes to aggressive phenotypes of cancer cells. The RAS-targeted therapies for cancer, therefore, have been recognised to be effective; however, current developments on targeting RAS have not advanced due to structural features of the RAS protein. Here, we show that expression of NRAS, a major isoform of RAS, can be controlled by photo-irradiation with an anionic phthalocyanine, ZnAPC, targeting NRAS mRNA. In vitro experiments reveal that ZnAPC binds to a G-quadruplex-forming oligonucleotide derived from the 5'-untranslated region of NRAS mRNA even in the presence of excess double-stranded RNA, which is abundant in cells, resulting in selective cleavage of the target RNA's G-quadruplex upon photo-irradiation. In line with these results, upon photo-irradiation, ZnAPC decreases NRAS mRNA and NRAS expression and thus viability of cancer cells. These results indicate that ZnAPC may be a prominent photosensitiser for a molecularly targeted photodynamic therapy for cancer.

リンク情報
DOI
https://doi.org/10.1038/s41467-018-04771-y
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29891945
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995912
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000434781600011&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/s41467-018-04771-y
  • ISSN : 2041-1723
  • PubMed ID : 29891945
  • PubMed Central 記事ID : PMC5995912
  • Web of Science ID : WOS:000434781600011

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