Liu Baihui, Cui Ximao, Zheng Shan, Dong Kuiran, Dong Rui
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, P.R. China.
Oncol Lett. 2017 Mar;13(3):1360-1364. doi: 10.3892/ol.2017.5558. Epub 2017 Jan 2.
DNA methylation has a crucial role in cancer biology and has been recognized as an activator of oncogenes and inactivator of tumor suppressor genes, both of which are mechanisms for tumorigenesis. Kallikrein-related peptidase 4 (KLK4), has been suggested to be an oncogene in various types of cancer. The aim of the present study was to assess the DNA methylation patterns of the KLK4 gene in cancerous samples harvested from patients with hepatoblastoma (HB). KLK4 mRNA expression levels were detected using reverse transcription-quantitative polymerase chain reaction and assessed its DNA methylation patterns using high-throughput mass spectrometry on a matrix-assisted laser desorption/ionization time-of-flight mass array. A total of 10 HB and 10 normal liver tissue samples were obtained from patients with HB. The results of the present study showed that a significantly higher level of KLK4 mRNA expression levels were detected in HB tissues, as compared with the matched controls. Furthermore, the KLK4 gene promoter region was distinctively less methylated in the HB samples compared with the controls and negatively correlated with KLK4 mRNA expression levels. These findings indicate that aberrant methylation of KLK4 may contribute to its upregulated mRNA expression in HB.
DNA甲基化在癌症生物学中起着至关重要的作用，并且已被认为是癌基因的激活剂和肿瘤抑制基因的失活剂，这两种都是肿瘤发生的机制。激肽释放酶相关肽酶4（KLK4）已被认为是多种类型癌症中的癌基因。本研究的目的是评估从肝母细胞瘤（HB）患者采集的癌组织样本中KLK4基因的DNA甲基化模式。使用逆转录-定量聚合酶链反应检测KLK4 mRNA表达水平，并在基质辅助激光解吸/电离飞行时间质谱阵列上使用高通量质谱法评估其DNA甲基化模式。共从HB患者中获取了10份HB组织样本和10份正常肝组织样本。本研究结果显示，与匹配的对照相比，在HB组织中检测到的KLK4 mRNA表达水平显著更高。此外，与对照相比，HB样本中KLK4基因启动子区域的甲基化明显较少，且与KLK4 mRNA表达水平呈负相关。这些发现表明，KLK4的异常甲基化可能导致其在HB中mRNA表达上调。
