Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes
Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes
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DOI：
10.3892/ijo.2016.3473
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发表时间：
2016-06-01
影响因子：
5.2
通讯作者：
Kim, Yong Sung
中科院分区：
文献类型：
--
作者：
Kim, Mirang;Kim, Jong-Hwan;Kim, Yong Sung
SLIT被认为是癌症发展的关键调节因子，也是癌症治疗的一个有前途的治疗靶点。在此，我们分析了SLIT 1/SLIT 2/SLIT 3在11个胃癌细胞系、96对胃肿瘤和癌旁正常胃组织以及250个由癌症基因组图谱提供的胃癌中的表达和甲基化。SLIT 1/SLIT 2/SLIT 3甲基化在早期胃癌和进展期胃癌中均有表达。甚至正常胃组织也显示SLIT 1和SLIT 3的甲基化增加，这与患者年龄相关。此外，SLIT的表观遗传失活以胃癌亚型依赖的方式发生。SLIT 2和SLIT 3的表达在EB病毒阳性和微卫星不稳定亚型中减少，但在基因组稳定亚型中增加。miR-218的表达与SLIT 2或SLIT 3的甲基化呈负相关。这些发现表明，在胃癌的治疗中，需要针对SLIT和miR-218的分子亚型特异性治疗策略。
SLIT has been suggested as a key regulator of cancer development and a promising therapeutic target for cancer treatment. Herein, we analyzed expression and methylation of SLIT1/SLIT2/SLIT3 in 11 gastric cancer cell lines, 96 paired gastric tumors and adjacent normal gastric tissues, and 250 gastric cancers provided by The Cancer Genome Atlas. Methylation of SLIT1/SLIT2/SLIT3 was found both in early gastric cancers, and in advanced gastric cancers. Even normal gastric tissue showed increased methylation of SLIT1 and SLIT3 that correlated with patient age. Furthermore, epigenetic inactivation of SLIT occurred in a gastric cancer subtype-dependent manner. SLIT2 and SLIT3 expression was reduced in Epstein-Barr virus-positive and microsatellite instability subtypes, but increased in the genomically stable subtype. Expression of miR-218 correlated negatively with methylation of SLIT2 or SLIT3. These findings suggest that a molecular subtype-specific therapeutic strategy is needed for targeting SLITs and miR-218 in treatment of gastric cancer.