A high-throughput screen identifies miRNA inhibitors regulating lung cancer cell survival and response to paclitaxel

• DOI: 10.4161/rna.26541
• Publication Date: 2013-10-24T16:52:12Z
• Authors: Liqin Du; Robert Borkowski; Zhenze Zhao; Xiuye Ma; Xiaojie Yu; Xian-Jin Xie; Alexander Pertsem...
• Keywords: 0301 basic medicine; Lung Neoplasms; Paclitaxel; Cell Survival; Caspases, Effector; Apoptosis; Antineoplastic Agents, Phytogenic; High-Throughput Screening Assays; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Antineoplastic Combined Chemotherapy Protocols; Humans

microRNAs (miRNAs) are small RNAs endogenously expressed in multiple organisms that regulate gene expression largely by decreasing levels of target messenger (mRNAs). Over the past few years, numerous studies have demonstrated critical roles for miRNAs pathogenesis many cancers, including lung cancer. Cellular miRNA can be easily manipulated, showing promise developing miRNA-targeted oligos as next-generation therapeutic agents. In a comprehensive effort to identify novel miRNA-based agents cancer treatment, we combined high-throughput screening platform with library chemically synthesized inhibitors systematically reduce cell survival and those sensitize cells paclitaxel. By three lines different genetic backgrounds, identified potentially universal cytotoxic effect on paclitaxel suggesting potential these We then focused characterizing (miR-133a/b, miR-361-3p, miR-346) most potent survival. two (miR-133a/b miR-361-3p) decrease activating caspase-3/7-dependent apoptotic pathways inducing cycle arrest S phase. Future certainly needed define mechanisms which drug response, explore translating current findings into clinical applications.