Kang Nahyeon, Choi Su Yeon, Kim Young Kyoon, Yoo Ie Ryung, Han Dae Hee, Lee Dong Soo, Kim Yeon Sil, Hong Sook Hee, Kang Jin Hyoung, Lee Kyo Young, Park Jae Kil, Sung Sook Whan, Park Mi Sun, Yim Hyeon Woo, Kim Seung Joon, Park Jong Y
The Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Lung Cancer. 2015 Aug;89(2):99-103. doi: 10.1016/j.lungcan.2015.05.011. Epub 2015 Jun 4.
Recent studies demonstrated that miR-137 is downregulated in various tumors, and that it functions as a tumor suppressor. miR-137 could be silenced by its aberrant promoter hypermethylation. The purpose of this study was to investigate the significance of MIR137 promoter methylation on its expression in lung cancer.
Lung cancer cell lines were treated with either a DNA methyltransferase inhibitor (5-azacytidine, AZA) and/or an HDAC inhibitor (trichostatin A, TSA) to determine whether miR-137 expression was reactivated. Paired lung tumor and adjacent non-tumor lung tissues were obtained (n=50). Quantitative methylation-specific PCR and bisulfite sequencing were used to analyze the methylation status of MIR137, and real-time RT-PCR was performed to analyze miR-137 expression.
miR-137 was reactivated by treatment with either AZA and/or TSA in lung cancer cell lines. Methylation-specific PCR showed increased MIR137 promoter methylation in lung tumors compared with adjacent non-tumor tissues, which was further validated by bisulfite sequencing. The expression of miR-137 was downregulated significantly in lung tumors, which was correlated with level of MIR137 promoter methylation inversely.
miR-137 downregulation was related to its promoter hypermethylation in lung cancer. Further studies are needed to assess its value as a prognostic factor and potential therapeutic applications in lung cancer.
近期研究表明，miR-137在多种肿瘤中表达下调，发挥肿瘤抑制作用。其异常的启动子高甲基化可导致miR-137沉默。本研究旨在探讨MIR137启动子甲基化对其在肺癌中表达的意义。
用DNA甲基转移酶抑制剂（5-氮杂胞苷，AZA）和/或组蛋白去乙酰化酶抑制剂（曲古抑菌素A，TSA）处理肺癌细胞系，以确定miR-137表达是否被重新激活。获取配对的肺肿瘤组织和相邻的非肿瘤肺组织（n = 50）。采用定量甲基化特异性PCR和亚硫酸氢盐测序分析MIR137的甲基化状态，并用实时RT-PCR分析miR-137的表达。
在肺癌细胞系中，用AZA和/或TSA处理可使miR-137重新激活。甲基化特异性PCR显示，与相邻非肿瘤组织相比，肺肿瘤中MIR137启动子甲基化增加，亚硫酸氢盐测序进一步验证了这一结果。肺肿瘤中miR-137的表达显著下调，且与MIR137启动子甲基化水平呈负相关。
肺癌中miR-137下调与其启动子高甲基化有关。需要进一步研究评估其作为预后因素的价值以及在肺癌中的潜在治疗应用。
