摘要
目的探讨含有Ly6/Plaur结构域的高度糖基化的磷脂酰肌醇锚定蛋白8(LYPD8)在结直肠癌(CRC)中的表达及其生物学功能。方法将收集自2015年3月至2016年9月在温州医科大学附属新昌医院的40例CRC患者的CRC组织与相应的癌旁结直肠组织以及正常结直肠组织进行比较,检测不同临床分期患者CRC组织中LYPD8 mRNA表达,STAT3、p65的磷酸化水平以及IL-6、TNF-α的分泌水平;同时利用真核表达载体(pIRES2)构建过表达LYPD8的质粒DNA,检测LYPD8过表达对CRC细胞增殖和迁移的影响。结果与正常组织和癌旁组织相比,Ⅰ、Ⅱ、Ⅲ期CRC患者癌组织中LYPD8 mRNA表达水平均明显降低(均P<0.05),其中Ⅲ期患者降低最明显(P<0.05)。CRC组织中STAT3/p65磷酸化水平及IL-6、TNF-α水平均明显增加(均P<0.05)。SW480细胞中LYPD8过表达,其存活凋亡百分比明显降低(P<0.05),迁移个数明显减少(P<0.05)。结论LYPD8在Ⅰ、Ⅱ、Ⅲ期患者CRC组织中的表达较癌旁组织及正常组织明显降低;LYPD8在CRC细胞中通过诱导STAT3、p65去磷酸化,抑制TNF-α、IL-6的分泌,从而抑制CRC细胞的增殖和迁移。
Objective To explore the expression and biological function of Ly6/plaur domain-containing protein 8(LYPD8)in colorectal cancer(CRC).Methods The expression of LYPD8 mRNA were detected in tumor tissue and pericancerous tissue samples of 40 CRC patients from March 2015 to September 2016 at the Affiliated Xinchang Hospital of Wenzhou Medical University,the phosphorylation levels of STAT3 and p65,the secretion levels of IL-6 and TNF-α were also detected.Human CRC SW480 cells were transfected with nuclear expression vector(pIRES2)and the proliferation and migration of SW480 cells overexpressing LYPD8 were determined.Results Compared with normal tissues and pericancerous tissues,the level of LYPD8 mRNA expression in CRC tissues of patients I,II,and III was significantly reduced(all P<0.05),and the reduction was most significant in patients with stage III(P<0.05).The phosphorylation level of STAT3/p65 and the levels of IL-6 and TNF-α in CRC tissues increased significantly(all P<0.05).LYPD8 was overexpressed in transfected SW480 cells,and its proliferation and apoptosis percentage were significantly reduced(P<0.05),and the number of migration was significantly decreased(P<0.05).Conclusion The expression of LYPD8 in CRC patients is significantly downregulated.LYPD8 can inhibit the proliferation and migration of CRC cells,also inhibit the secretion of TNF-α and IL-6 by inducing STAT3 and p65 dephosphorylation in CRC cells.
作者
钱峻
严富国
陈文山
陈允
黄海平
叶明燕
QIAN Jun;YAN Fuguo;CHEN Wenshan;CHEN Yun;HUANG Haiping;YE Mingyan(Department of General Surgery,Affiliated Xinchang Hospital of Wenzhou Medical University,Xinchang 312500,China)
出处
《浙江医学》
CAS
2020年第19期2042-2046,I0003,共6页
Zhejiang Medical Journal
基金
浙江省医药卫生科技计划面上项目(2019KY737)。
