Li Dongsheng, Guo Jialin, Wang Song, Zhu Liangchen, Shen Zugang
Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China.
Oncol Lett. 2017 Sep;14(3):2643-2648. doi: 10.3892/ol.2017.6506. Epub 2017 Jun 30.
The present study was conducted to investigate novel methylated targets in colorectal cancer (CRC). The mRNA expression profiles of GSE32323 in 17 cancer and non-cancerous tissues from CRC patients, as well as expression profiles of 5 CRC cell lines prior and subsequent to 5-aza-2'-deoxycytidine (5-aza-dC) treatment, were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in 5 CRC cell lines prior and subsequent to 5-aza-dC treatment were combined with the CRC-specific gene expression profiling array data. Context likelihood of relatedness algorithm was used to construct the co-expression network of CRC-specific gene expression profile. A sub-network of identified reverse-overlapped DEGs was selected and underwent Kyoto Encyclopedia of Genes and Genomes Pathway Analysis. A total of 6 reverse-overlapped DEGs were identified. This present study verified fibulin 2 (FBLN2) and protein phosphatase 1 regulatory inhibitor subunit 14A (PPP1R14A) to be downregulated in the CRC tissue sample but upregulated in CRC cell lines following 5-aza-dC treatment. The identified reverse-overlapped DEGs were enriched in tumor-associated signaling pathways, including cellular tumor antigen p53, cell cycle and NOD-like receptor (NLR) signaling pathway. A total of 2 silenced genes with abnormal methylation in CRC were identified, including FBLN2 and PPP1R14A. The reverse-overlapped DEGs were enriched in p53, cell cycle and NLR signaling pathways, indicating that reverse-overlapped DEGs, particularly FBLN2 and PPP1R14A, may be important tumor suppressors and that these reverse-overlapped DEGs are inactivated by methylation in CRC.
本研究旨在探究结直肠癌（CRC）中的新型甲基化靶点。从基因表达综合数据库中获取了17例CRC患者癌组织和癌旁组织的GSE32323 mRNA表达谱，以及5种CRC细胞系在5-氮杂-2'-脱氧胞苷（5-aza-dC）处理前后的表达谱。将5种CRC细胞系在5-aza-dC处理前后的差异表达基因（DEG）与CRC特异性基因表达谱阵列数据相结合。使用关联上下文似然算法构建CRC特异性基因表达谱的共表达网络。选择鉴定出的反向重叠DEG的一个子网并进行京都基因与基因组百科全书通路分析。共鉴定出6个反向重叠DEG。本研究证实，在CRC组织样本中，纤连蛋白2（FBLN2）和蛋白磷酸酶1调节抑制亚基14A（PPP1R14A）表达下调，但在5-aza-dC处理后的CRC细胞系中表达上调。鉴定出的反向重叠DEG富集于肿瘤相关信号通路，包括细胞肿瘤抗原p53、细胞周期和NOD样受体（NLR）信号通路。共鉴定出2个在CRC中甲基化异常的沉默基因，包括FBLN2和PPP1R14A。反向重叠DEG富集于p53、细胞周期和NLR信号通路，表明反向重叠DEG，特别是FBLN2和PPP1R14A，可能是重要的肿瘤抑制因子，且这些反向重叠DEG在CRC中因甲基化而失活。
