MicroRNAs (miRNAs) are endogenous small non-coding RNAs composed of 20∼25 base pairs that can negatively regulate gene expression by interfering with the translation of target transcripts. Since it has been known that some miRNAs function as tumor suppressors (TS) and their expression levels are often down-regulated in cancer, TS-miRNAs are expected to be therapeutic agents for cancer therapy. Thus, we conducted function-based screening using a miRNA library, and identified several TS-miRNAs, including miR-152, miR-218, miR-596.
Recently, we identified miR-634 as a new TS-miRNA, which induced cell death with mitochondrial dysfunction and caspase activation. The expression analysis and the target-prediction program revealed miR-634 might directly target genes related with anti-apoptosis and mitochondrial function.
Importantly, this miRNA was frequently down-regulated in primary tumor samples of esophageal squamous cell carcinoma (ESCC), compared with that in corresponding normal tissues. Furthermore, the combination therapy of miR-634 and cisplatin was effective to ESCC cell line in vitro and in vivo. Thus, these findings suggest that miR-634 may be useful as a potential therapeutic agent of ESCC.
Citation Format: Naoto Fujiwara, Jun Inoue, Tatsuyuki Kawano, Ken-ichi Kozaki, Johji Inazawa. MicroRNA-634 induces caspase-dependent apoptosis by targeting anti-apopotic and mitochondria-related genes in human cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5200. doi:10.1158/1538-7445.AM2014-5200