MicroRNAs and Their Therapeutic Potential for Human Diseases: MicroRNAs, miR-143 and -145, Function as Anti-oncomirs and the Application of Chemically Modified miR-143 as an Anti-cancer Drug

• Kitade Yukio

  United Graduate School of Drug Discovery and Medicinal Information Sciences, Gifu University, Japan Center for Advanced Drug Research, Gifu University, Japan Department of Biomolecular Science, Faculty of Engineering, Gifu University, Japan

• Akao Yukihiro

  United Graduate School of Drug Discovery and Medicinal Information Sciences, Gifu University, Japan Center for Advanced Drug Research, Gifu University, Japan

Bibliographic Information

Other Title

• MicroRNAs, miR-143 and -145, function as anti-oncomirs and the application of chemically modified miR-143 as an anti-cancer drug

Abstract

We examined the expression levels of microRNAs (miRNAs; miRs) in colorectal tumors (63 cancer specimens and 65 adenoma specimens) compared to adjacent non-tumorous tissues. Decreased expression of miR-143 and -145 was frequently observed in the adenoma and cancer samples. As the down-regulation of miR-143 and -145 was observed even in the early phase of adenoma formation, their decreased expression would appear to contribute mainly to the initiation of tumorigenesis. For clinical application, we added aromatic benzene-pyridine (BP-type) analogs to the 3′-overhang region of the RNA-strand and changed the sequences of the passenger strand in the miR-143 duplex (miR-143BPs), leading to greater activity and increased resistance to nuclease. The cell growth inhibitory effect of the chemically modified miR-143BPx in vitro was greater than that of the endogenous miR-143. The modified miR-143BPx showed a significant tumor-suppressive effect on xenografted tumors of human colorectal cancer DLD-1 cells. These findings suggest that miR-143 and -145 are important onco-related genes for the initiation of colorectal tumor development and that chemically modified miR-143BPx may be a candidate for an RNA medicine for the treatment of colorectal tumors.

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 114 (3), 276-280, 2010

  The Japanese Pharmacological Society

Keywords

• colorectal tumor
• miR-143
• miR-145
• chemically modified microRNA
• xenografted tumor
• tumor suppression

Details

• CRID: 1390001205180625920
• NII Article ID: 10029890344
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.10r12fm
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 10887869
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10887869
• Web Site: https://search.jamas.or.jp/link/ui/2011206298
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed