J Cancer 2016; 7(6):656-663. doi:10.7150/jca.13674

Research Paper

MicroRNA-874 Functions as a Tumor Suppressor by Targeting Cancer/Testis Antigen HCA587/MAGE-C2

Xiao Song*, Wenjie Song*, Ying Wang, Jingjing Wang, Yan Li, Xiaoping Qian, Xuewen Pang, Yu Zhang, Yanhui Yin

Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, Beijing, China.
*These authors contributed equally to this work.

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Song X, Song W, Wang Y, Wang J, Li Y, Qian X, Pang X, Zhang Y, Yin Y. MicroRNA-874 Functions as a Tumor Suppressor by Targeting Cancer/Testis Antigen HCA587/MAGE-C2. J Cancer 2016; 7(6):656-663. doi:10.7150/jca.13674. Available from http://www.jcancer.org/v07p0656.htm

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Cancer/testis antigen HCA587/MAGE-C2 has been considered as a tumor specific target for immunotherapy. It has been reported that HCA587/MAGE-C2 plays an active role in tumorigenesis by promoting the growth and survival of tumor cells. However, the regulation of HCA587/MAGE-C2 expression in cancer cells remains largely unknown. MicroRNAs (miRNAs), a large family of gene regulators, have been shown to negatively regulate the expression of important cancer-related genes and contribute to the initiation and development of cancers. In this study, we conducted searches of miRNAs that regulate HCA587/MAGE-C2 expression. We combined bioinformatics tools with biological validation assays to demonstrate that HCA587/MAGE-C2 is a direct target of microRNA-874 (miR-874). Furthermore, we investigated the expression levels of miR-874 in human hepatocellular carcinoma tissues and paired adjacent normal tissues by stem-loop reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results revealed a significant downregulation of miR-874 expression in tumor tissues compared to adjacent normal tissues. Finally, we demonstrated that overexpression of miR-874, as well as HCA587/MAGE-C2 silencing, resulted in suppression of tumor cell proliferation and invasion. Moreover, the inhibition effects of miR-874 on cell proliferation and invasion were reversed by co-expression of HCA587/MAGE-C2 in A375 cells. Taken together, our data demonstrated that HCA587/MAGE-C2 is a direct target of miR-874, and miR-874 may function as a tumor suppressive miRNA, at least in part, by negatively regulating HCA587/MAGE-C2 expression in cancer cells.

Keywords: Cancer/testis antigen, HCA587/MAGE-C2, MiRNA-874, Cell proliferation, Cell invasion.