MicroRNA-708-5p acts as a therapeutic agent against metastatic lung cancer
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Xiaoping Wu1, Tianchi Liu1, Ou Fang1, Wenhua Dong1, Fengjun Zhang1, Lindsey Leach2, Xiaohua Hu1, Zewei Luo1,2
1Laboratory of Population and Quantitative Genetics, Institute of Biostatistics, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
2School of Biosciences, University of Birmingham, Birmingham, UK
Zewei Luo, e-mail: [email protected]
Xiaohua Hu, e-mail: [email protected]
Keywords: non-small cell lung cancer, therapeutic agent, MicroRNA-708-5p, metastasis, p21
Received: August 10, 2015 Accepted: November 21, 2015 Published: December 14, 2015
MicroRNAs (miRNAs) have recently been recognized as targets for anti-metastatic therapy against cancer malignancy. Development of effective miRNA mediated therapies remains a challenge to both basic research and clinical practice. Here we presented the evidence for a miR-708-5p mediated replacement therapy against metastatic lung cancer. Expression of miR-708-5p was substantially reduced in metastatic lung cancer samples and cancer cell lines when compared to non-metastatic counterparts. Expression of the miRNA suppressed cell survival and metastasis in vitro through its direct target p21, and inhibited the PI3K/AKT pathway and stem cell-like characteristics of lung cancer cells. Systemic administration of this miRNA in a mouse model of NSCLC using polyethylenimine (PEI)-mediated delivery of unmodified miRNA mimics induced tumor specific apoptosis. It also effectively protected the tested animals from developing metastatic malignancy without causing any observed toxicity. The findings strongly support miR-708-5p as a novel and effective therapeutic agent against metastatic malignancy of non-small cell lung cancer.
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