Lv Yan, Song Yu, Ni Chen, Wang Shaokai, Chen Zhipeng, Shi Xiaojing, Jiang Qin, Cao Cong, Zuo Yun
Center of Translational Medicine, The First People Hospital of Zhangjiagang City, Soochow University, Suzhou, China.
Department of Oncology, The First People Hospital of Zhangjiagang City, Soochow University, Suzhou, China.
Cell Physiol Biochem. 2018;45(3):1219-1229. doi: 10.1159/000487453. Epub 2018 Feb 9.
BACKGROUND/AIMS: Lymphocyte antigen 6 complex, locus E (LY6E) is a member of the lymphostromal cell membrane Ly6 superfamily protein. The present study investigated the clinical significance and potential biological function of LY6E in gastric cancer (GC).
LY6E mRNA and protein expressions in human GC tissues and GC cells were tested. Relationship between LY6E expression and the GC patients' clinicopathologic characteristics was analyzed. LY6E was silenced by siRNA in the cultured GC cells.
The RNA expression microarray profiling assay results demonstrated that LY6E mRNA was significantly increased in multiple human GC tumor tissues. Immunohistochemistry (IHC) staining analysis revealed that 59 of 75 (78.7%) GC specimens were LY6E positive. LY6E over-expression in human GC was correlated with the histology grade, AJCC stage, N classification, lymphatic invasion, and tumor location. Notably, functional LY6E expression was also detected in AGS and other established GC cell lines. LY6E knockdown by targeted-siRNA inhibited AGS cell survival and proliferation. Meanwhile, the LY6E siRNA induced G1-S cell cycle arrest and apoptosis in AGC cells. Additionally, AGC cell migration was also inhibited by LY6E knockdown. Expressions of tumor-suppressing proteins, including PTEN (phosphatase and tensin homolog) and E-Cadherin, were increased in LY6E-silenced AGS cells.
LY6E over-expression in GC is potentially required for cancer cell survival, proliferation and migration.
背景/目的：淋巴细胞抗原6复合体E位点（LY6E）是淋巴基质细胞膜Ly6超家族蛋白的成员。本研究探讨LY6E在胃癌（GC）中的临床意义及潜在生物学功能。
检测人GC组织和GC细胞中LY6E mRNA和蛋白表达。分析LY6E表达与GC患者临床病理特征的关系。在培养的GC细胞中用小干扰RNA（siRNA）沉默LY6E。
RNA表达微阵列分析结果显示，多种人GC肿瘤组织中LY6E mRNA显著增加。免疫组织化学（IHC）染色分析显示，75例GC标本中有59例（78.7%）LY6E呈阳性。人GC中LY6E的过表达与组织学分级、美国癌症联合委员会（AJCC）分期、N分类、淋巴浸润和肿瘤位置相关。值得注意的是，在AGS及其他已建立的GC细胞系中也检测到功能性LY6E表达。靶向siRNA敲低LY6E可抑制AGS细胞存活和增殖。同时，LY6E siRNA诱导AGS细胞G1-S期细胞周期阻滞和凋亡。此外，敲低LY6E也抑制了AGS细胞迁移。在LY6E沉默的AGS细胞中，包括磷酸酶和张力蛋白同源物（PTEN）和E-钙黏蛋白在内的抑癌蛋白表达增加。
GC中LY6E的过表达可能是癌细胞存活、增殖和迁移所必需的。
