School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
Medical Genetics Center, School of Medicine, Ningbo University, Ningbo 315211, China.
Zhongguo Fei Ai Za Zhi. 2022 Feb 20;25(2):78-85. doi: 10.3779/j.issn.1009-3419.2022.102.03.
The occurrence and development of lung cancer are closely linked to epigenetic modification. Abnormal DNA methylation in the CpG island region of genes has been found in many cancers. Protein kinase C delta binding protein (PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies. This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer (NSCLC).
We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues. Promoter activity was measured by the dual luciferase assay, with 5'-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP.
The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant (>10 cm) non-tumor tissues. Receiver operating characteristic (ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line (AUC) was 0.717. Dual luciferase experiment confirmed that the promoter region was able to promote gene expression. Meanwhile, in vitro methylation of the fragment (PRKCDBP_Me) could significantly reduce the promoter activity of the fragment. Demethylation of 5'-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels.
PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer.
肺癌的发生和发展与表观遗传修饰密切相关。在许多癌症中，基因 CpG 岛区域的异常 DNA 甲基化已经被发现。蛋白激酶 C 德尔塔结合蛋白（PRKCDBP）是一种潜在的肿瘤抑制因子，其表观遗传变化在许多人类恶性肿瘤中都有发现。本研究探讨了 PRKCDBP 甲基化作为非小细胞肺癌（NSCLC）潜在生物标志物的可能性。
我们测量了三组 NSCLC 组织中 PRKCDBP 的甲基化水平。通过双荧光素酶检测来测量启动子活性，并用 5'-氮杂-2'-脱氧胞苷来检测去甲基化对 PRKCDBP 表达水平的影响。
肿瘤组织和 3cm 旁肿瘤组织的 PRKCDBP 甲基化水平高于远处（>10cm）非肿瘤组织。肿瘤组织与远处非肿瘤组织之间的接收者操作特征（ROC）曲线分析显示，曲线下面积（AUC）为 0.717。双荧光素酶实验证实启动子区域能够促进基因表达。同时，体外对片段（PRKCDBP_Me）进行甲基化可以显著降低片段的启动子活性。肺癌细胞系 A549 和 H1299 中的 5'-氮杂-2'-脱氧胞苷去甲基化显示 PRKCDBP mRNA 水平显著上调。
PRKCDBP 甲基化是一种有潜力和有前途的非小细胞肺癌候选生物标志物。
