2018年6月11日
An anionic phthalocyanine decreases NRAS expression by breaking down its RNA G-quadruplex.
Nature communications
- 巻
- 9
- 号
- 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