Abstract 1402: Preclinical evaluation of a novel senescence-associated miRNA miR-3140-3p for malignant pleural mesothelioma

Abstract

Abstract Cellular senescence acts as a natural barrier against tumor progression Our previous study showed that selective induction of senescence using miR-22, one of senescence-associated microRNAs (SA-miRNAs), suppressed tumor progression (JCB 2011) In this study, we developed functional screening system using miRNA library to identify a potent SA-miRNA that suppress malignant tumor such as anti-cancer drug resistant and cancer stem cells. We focused on microRNA inducing the senescent phenotype in normal human fibroblast cell After transfection of 2028 miRNA mimics library in normal human fibroblast TIG-3, we evaluate the senescence phenotypes such as cell growth arrest and size enlargement using high content analyzer, and found that 349 miRNAs induced cellular senescence More importantly, we identified miR-3140-3p as potent SA-miRNA that significantly suppressed tumor cell proliferation in several types of cancer cells including cancer stem cells and anti-cancer drug resistant cells. We focused on malignant pleural mesothelioma (MPM) which is an aggressive tumor developed from the mesothelial lining cells of the pleura MPM is caused by direct asbestos exposure and is an incurable tumor type for the lack of effective treatment In addition, as Japan is one of the world's highest importers and users of asbestos, the cases of mesothelioma are expected to increase in the near future Therefore, we investigated the possibility of whether SA-miRNAs showed tumor suppressive effects against MPM cell lines Moreover, we tried to develop a new treatment or medicine for the MPM patients using SA-miRNA In vitro and in vivo analysis revealed that several SA-miRNAs drastically suppressed the tumor cell proliferation Based on these findings, the modulation of SA-miRNA is a promising approach to improve the treatment of MPM patients In addition, we performed and completed pre-clinical trials and design first-in-human study in Japan. Citation Format: Yuki Yamamoto, Ayaka Nishiura, Kimiyoshi Yano, Noriaki Matsuda, Ryou-u Takahashi, Yasuhiro Tsutani, Morihito Okada, Hidetoshi Tahara. Preclinical evaluation of a novel senescence-associated miRNA miR-3140-3p for malignant pleural mesothelioma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1402.