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microRNA-34a as a Therapeutic Agent against Human Cancer

Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan
Author to whom correspondence should be addressed.
Academic Editors: Takahiro Ochiya and Ryou-u Takahashi
J. Clin. Med. 2015, 4(11), 1951-1959;
Received: 20 October 2015 / Revised: 5 November 2015 / Accepted: 9 November 2015 / Published: 16 November 2015
(This article belongs to the Special Issue MicroRNAs: Novel Biomarkers and Therapeutic Targets for Human Cancers)
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. View Full-Text
Keywords: microRNA; miR-34a; cancer; cancer stem cell; DNA methylation microRNA; miR-34a; cancer; cancer stem cell; DNA methylation
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Saito, Y.; Nakaoka, T.; Saito, H. microRNA-34a as a Therapeutic Agent against Human Cancer. J. Clin. Med. 2015, 4, 1951-1959.

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