ABSTRACT

Gastric cancer is one of the most frequently diagnosed malignant tumors, with rapid progression and poor prognosis. The role of chondroitin sulfate synthase 1 (CHSY1) in the development and progression of gastric cancer was explored and clarified in this study. The immunohistochemistry analysis of clinical tissue samples as well as data mining of public database showed that CHSY1 was significantly upregulated in gastric cancer and associated with more advanced tumor stage and poorer prognosis. In vitro loss-of-function experiments demonstrated the inhibited cell proliferation, colony formation, cell migration, as well as the promoted cell apoptosis by CHSY1 knockdown. Moreover, recovery of CHSY1 expression could attenuate the regulatory effects induced by CHSY1 knockdown. Correspondingly, gastric cancer cells with CHSY1 knockdown showed reduced tumorigenicity and slower tumor growth in vivo. In conclusion, this study identified CHSY1 as a tumor promotor in gastric cancer, which may be utilized as a novel indicator of patients’ prognosis and therapeutic target for developing more effective drug for GC treatment.

摘要

胃癌是最常见的恶性肿瘤之一，病情进展快，预后差。本研究探讨并阐明了硫酸软骨素合酶 1 (CHSY1) 在胃癌发生发展中的作用。临床组织样本的免疫组化分析以及公共数据库的数据挖掘表明，CHSY1在胃癌中显着上调，并且与更晚期的肿瘤分期和更差的预后相关。体外功能丧失实验表明 CHSY1 敲低可抑制细胞增殖、集落形成、细胞迁移以及促进细胞凋亡。此外，CHSY1 表达的恢复可以减弱 CHSY1 敲低诱导的调节作用。相应地，具有 CHSY1 敲低的胃癌细胞在体内显示出降低的致瘤性和较慢的肿瘤生长。总之，本研究确定 CHSY1 是胃癌的肿瘤促进剂，可作为患者预后的新指标和治疗靶点，用于开发更有效的 GC 治疗药物。