Wu Yuan-Yu, Jiang Jun-Nan, Fang Xue-Dong, Ji Fu-Jian
Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Front Physiol. 2018 Aug 21;9:1132. doi: 10.3389/fphys.2018.01132. eCollection 2018.
In China, majority of the mortality in gastric cancer are associated with peritoneal metastasis. Since most gastric tumors are metastatic at initial diagnosis, the treatment of gastric cancer is limited to radical resection. Therefore, it is imperative to identify diagnostic and prognostic biomarkers. From 2014 to 2015, 20 patients were enrolled in the study. To search translationally upregulated genes in the context of epithelial to mesenchymal transition (EMT), polysome profiling was performed. The MTT, migration, and invasion assay were conducted to determine cell proliferation, migration, and invasion ability respectively. Experiments of gain and loss of function were performed using the overexpression plasmid, siRNA, and shRNA. Xenograft assay was established using nude mice to explore the role of targets translationally upregulated gene . Polysome profiling defined the landscape of translationally regulated gene products with differential expression between non-metastatic and metastatic cohorts. Six-transmembrane epithelial antigen of the prostate 1 () was found to be the most translationally upregulated gene product in either experimental groups. was found to be required for cell proliferation, migration and invasion, and tumorigenesis. RNAi-mediated silencing of potentiated chemosensitivity of the MKN45 cells to docetaxel treatment, highlighting the importance of as a novel biomarker in gastric cancer patients with peritoneal metastasis. is thus induced translationally and its expression promotes proliferation, migration, invasiveness, and tumorigenicity of gastric cancer. can be a potent candidate for designing of targeted therapy.
在中国，胃癌的大多数死亡与腹膜转移相关。由于大多数胃肿瘤在初次诊断时就已发生转移，胃癌的治疗仅限于根治性切除。因此，识别诊断和预后生物标志物势在必行。2014年至2015年，20名患者被纳入该研究。为了在上皮-间质转化（EMT）背景下寻找翻译上调基因，进行了多核糖体谱分析。分别进行MTT、迁移和侵袭试验以确定细胞增殖、迁移和侵袭能力。使用过表达质粒、小干扰RNA（siRNA）和短发夹RNA（shRNA）进行功能获得和功能丧失实验。利用裸鼠建立异种移植试验以探索翻译上调基因靶点的作用。多核糖体谱分析确定了非转移组和转移组之间具有差异表达的翻译调控基因产物的情况。前列腺六跨膜上皮抗原1（）被发现是两个实验组中翻译上调最明显的基因产物。被发现是细胞增殖、迁移、侵袭以及肿瘤发生所必需的。RNA干扰介导的沉默增强了MKN45细胞对多西他赛治疗的化疗敏感性，突出了作为腹膜转移胃癌患者新型生物标志物的重要性。因此是翻译诱导的，其表达促进胃癌的增殖、迁移、侵袭性和肿瘤发生。可成为设计靶向治疗的有力候选者。
