Overexpression of Lymphocyte Antigen 6 Complex, Locus E in Gastric Cancer Promotes Cancer Cell Growth and Metastasis
Overexpression of Lymphocyte Antigen 6 Complex, Locus E in Gastric Cancer Promotes Cancer Cell Growth and Metastasis
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胃癌中淋巴细胞抗原6复合物E位点的过度表达促进癌细胞生长和转移
DOI：
10.1159/000487453
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Zuo, Yun
中科院分区：
文献类型：
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作者：
Lv, Yan;Song, Yu;Zuo, Yun
淋巴细胞抗原6复合物E位点（LY 6 E）是淋巴基质细胞膜Ly 6超家族蛋白的一员。本研究旨在探讨LY 6 E在胃癌中的临床意义及潜在的生物学功能。方法：检测人胃癌组织和胃癌细胞中LY 6 E mRNA和蛋白的表达。分析LY 6 E表达与胃癌临床病理特征的关系。在培养的GC细胞中，LY 6 E被siRNA沉默。结果如下：RNA表达谱芯片分析结果表明，LY 6 E mRNA在多种人胃癌组织中显著增加。免疫组化染色结果显示，75例胃癌中59例（78.7%）为LY 6 E阳性。LY 6 E在人胃癌中的过表达与组织学分级、AJCC分期、N分类、淋巴管浸润和肿瘤部位相关。值得注意的是，在AGS和其他建立的GC细胞系中也检测到功能性LY 6 E表达。通过靶向siRNA敲低LY 6 E抑制AGS细胞存活和增殖。同时，LY 6 E siRNA可诱导AGC细胞发生G1-S期阻滞和凋亡。此外，AGC细胞的迁移也受到抑制LY 6 E敲低。在LY 6 E沉默的AGS细胞中，肿瘤抑制蛋白，包括PTEN（磷酸酶和张力蛋白同源物）和E-Cadherin的表达增加。结论：LY 6 E在胃癌中的过表达可能是癌细胞存活、增殖和迁移所必需的。
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). Methods: 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. Results: 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. Conclusion: LY6E over-expression in GC is potentially required for cancer cell survival, proliferation and migration.