Zhang Hui, Xu Chenxin, Shi Chen, Zhang Junying, Qian Ting, Wang Zhuo, Ma Rong, Wu Jianzhong, Jiang Feng, Feng Jifeng
Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
Research Center for Clinical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting, Nanjing, 210000, Jiangsu, People's Republic of China.
J Transl Med. 2021 Mar 5;19(1):98. doi: 10.1186/s12967-021-02770-0.
The epigenetic abnormality of tumor-associated genes contributes to the pathogenesis of colorectal carcinoma (CRC). However, methylation in colorectal cancer is still poorly characterized.
By integration of DNA methylation data from the GEO database and gene expression data from The Cancer Genome Atlas database, the aberrantly methylated genes involved in CRC tumorigenesis were identified. Subsequent in vitro experiments further validated their role in CRC.
We performed integrative genomic analysis and identified HPSE2, a novel tumor suppressor gene that is frequently inactivated through promoter methylation in CRC. K-M survival analysis showed that hypermethylation-low expression of heparanase 2 (HPSE2) was related to poor patient prognosis. Overexpression of HPSE2 reduced cell proliferation in vivo and in vitro. HPSE2 could regulate the p53 signaling pathway to block the cell cycle in G1 phase.
HPSE2, a novel tumor suppressor gene that is frequently inactivated through promoter methylation in CRC. HPSE2 performs a tumor suppressive function by activating the p53/ p21 signaling cascade. The promoter hypermethylation of HPSE2 is a potential therapeutic target in patients with CRC, especially those with late-stage CRC.
肿瘤相关基因的表观遗传异常促成了结直肠癌（CRC）的发病机制。然而，结直肠癌中的甲基化特征仍不清楚。
通过整合来自基因表达综合数据库（GEO数据库）的DNA甲基化数据和来自癌症基因组图谱数据库（The Cancer Genome Atlas数据库）的基因表达数据，鉴定出参与结直肠癌发生的异常甲基化基因。随后的体外实验进一步验证了它们在结直肠癌中的作用。
我们进行了综合基因组分析，鉴定出HPSE2，这是一种新的肿瘤抑制基因，在结直肠癌中经常通过启动子甲基化而失活。K-M生存分析表明，乙酰肝素酶2（HPSE2）的高甲基化低表达与患者预后不良有关。HPSE2的过表达在体内和体外均降低了细胞增殖。HPSE2可调节p53信号通路，使细胞周期阻滞在G1期。
HPSE2是一种新的肿瘤抑制基因，在结直肠癌中经常通过启动子甲基化而失活。HPSE2通过激活p53/p21信号级联发挥肿瘤抑制功能。HPSE2启动子高甲基化是结直肠癌患者，尤其是晚期结直肠癌患者的潜在治疗靶点。
