microRNA-34a as a Therapeutic Agent against Human Cancer

Journal of Clinical Medicine

Yoshimasa Saito¹  Toshiaki Nakaoka²  Hidetsugu Saito²  Takahiro Ochiya² 

[1] Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan;

关键词: microRNA;    miR-34a;    cancer;    cancer stem cell;    DNA methylation;   

DOI  :  10.3390/jcm4111951

来源: mdpi

【 摘 要 】

microRNAs (miRNAs) are small non-coding RNAs that down-regulate expression of various target genes. Cancer-related miRNAs are aberrantly expressed and act as tumor suppressors or oncogenes during carcinogenesis. We and other researchers have demonstrated that important tumor suppressor miRNAs are silenced by epigenetic alterations, resulting in the activation of target oncogenes in cancer cells. miR-34a was identified as a target of p53 and induces a G1 cell cycle arrest, senescence and apoptosis in response to DNA damage. miR-34a is an important tumor suppressor whose expression is epigenetically silenced in various human cancers. Enforced expression of miR-34a induces cell cycle arrest, apoptosis, senescence, and suppression of epithelial-mesenchymal transition and inhibits cell proliferation of cancer stem cells. Epigenetic therapy with chromatin-modifying drugs such as inhibitors of DNA methylation and histone deacetylase has shown clinical promise for the treatment of malignancies. Restoring of miR-34a expression by epigenetic therapy and/or delivery of miR-34a mimics may be a promising therapeutic strategy against human cancer.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.