J Cancer 2016; 7(6):656-663. doi:10.7150/jca.13674
MicroRNA-874 Functions as a Tumor Suppressor by Targeting Cancer/Testis Antigen HCA587/MAGE-C2
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.
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
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.