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

ABSTRACT: 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.

SUBMITTER: Song X

PROVIDER: S-EPMC4829551 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Song Xiao X Song Wenjie W Wang Ying Y Wang Jingjing J Li Yan Y Qian Xiaoping X Pang Xuewen X Zhang Yu Y Yin Yanhui Y

Journal of Cancer 20160320 6

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 initia ...[more]

PMID: 27076846

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Project description:BACKGROUND:Discoidin domain receptor-1 (DDR1) tyrosine kinase is highly expressed in a variety of human cancers and involved in various steps of tumorigenesis. However, the precise mechanisms underlying the abnormal expression of DDR1 in oral squamous cell carcinoma (OSCC) has not been well investigated. METHODS:The expression of DDR1 on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-486-3p and DDR1 were accessed by MTT and Annexin V analyses using gain- and loss-of-function approaches. Chromatin immunoprecipitation (ChIP) and methylation specific PCR (MSP) were performed to explore the molecular mechanisms by arecoline treatment. RESULTS:Here, we reported that DDR1 was significantly upregulated in OSCC tissues and its levels were inversely correlated with miR-486-3p expression. The experimental results in vitro confirmed that miR-486-3p decreased DDR1 expression by targeting the 3'-UTR of DDR1 mRNA. Overexpression of miR-486-3p led to growth inhibition and apoptosis induction with a similar function by knockdown of DDR1. Aberrant methylation of ANK1 promoter was a highly prevalent in OSCC and contributes to oral carcinogenesis by epigenetic silencing of ANK1 and miR-486-3p. We found that miR-486-3p can be transcriptionally co-regulated with its host gene ANK1 through epigenetic repression. DNA methylation inhibitor treatment re-expressed ANK1 and miR-486-3p. Importantly, arecoline, a major betel nut alkaloid, recruited DNMT3B binding to ANK1 promoter for DNA methylation and then attenuated the expression of miR-486-3p in OSCC. CONCLUSION:This study was the first to demonstrate that betel nut alkaloid may recruit DNMT3B to regulate miR-486-3p/DDR1 axis in oral cancer andmiR-486-3p and DDR1 may serve as potential therapeutic targets of oral cancer.

Dataset Information

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

Publications

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

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