講演情報
[S18-3]腫瘍抑制型マイクロRNAの同定とがん治療への応用
○稲澤 譲治 (東京医科歯科大学リサーチコアセンター)
MicroRNAs (miRNA; miR) are small protein non-coding RNAs of approximately 22 nucleotides negatively regulating target-gene expression. In the last decade, we identified over 20 novel TS-miRs in various cancers using function-based screening with miR-libraries. Among those, miR-634 activates the apoptotic pathway by directly concurrent targeting of genes associated with mitochondrial homeostasis, anti-apoptosis, antioxidant ability, and autophagy. Overexpression of miR-634 strongly induced apoptosis by directly targeting multiple genes associated with mitochondrial biogenesis and cytoprotective processes against apoptosis in cancer cells. The enforced expression of miR-634 using chemically modified double-strand miR-634 mimics markedly enhanced chemotherapy-induced cytotoxicity in cancer cells in vitro and in vivo. We investigated the therapeutic potential of miR-634 ointment in subcutaneous xenograft tumors in nude mice and a mice model of cutaneous squamous cell carcinoma (CSCC). In xenograft tumors of A431 cells, a human skin SCC cell line, the topical treatment of ointment incorporated double-strand miR-634 mimics significantly reduced tumor growth. Furthermore, the topical treatment of miR-634 ointment also inhibited tumor growth in carcinogen-induced mouse skin papilloma model. These findings suggest that topical treatment of miR-634-ointment may be useful as a noninvasive and effective treatments for CSCC as well as other types of skin-invasive cancers.