Yan Dongmei, Tu Linglan, Yuan Haining, Fang Jianfei, Cheng Liyan, Zheng Xiaoliang, Wang Xiaoju
The Center for Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, 310013, Zhejiang, China.
Sci Rep. 2017 Nov 13;7(1):15443. doi: 10.1038/s41598-017-15749-z.
Human WBSCR22 gene is involved in tumor metastasis, cell growth and invasion, however, its role in chemosensitivity to antitumor agents remains unknown. In this study, we analyzed the TCGA cohort and found the expression of WBSCR22 was significantly elevated in human colorectal cancer (CRC) tissue. WBSCR22 could be served as an independent risk predictor for overall survival (OS), and up-regulated WBSCR22 could predict unfavorable OS for CRC patients. Knockdown of WBSCR22 significantly sensitized CRC cells to oxaliplatin in vitro and in vivo, while overexpression of WBSCR22 led to cellular resistance to oxaliplatin treatment. Although WBSCR22 knockdown did not change cell cycle, it increased the oxaliplatin-induced cellular apoptosis. WBSCR22 knockdown augmented the oxaliplatin-induced intracellular reactive oxygen species (ROS) production and ROS-induced 8-oxoguanine (8-oxoG) oxidative lesion accumulation, likely sensitizing oxaliplatin treatment. These results demonstrate that WBSCR22 is involved in CRC resistance to oxaliplatin, suggesting WBSCR22 may represent a novel oxaliplatin resistance biomarker as well as a potentail target for CRC therapeutics.
人类WBSCR22基因参与肿瘤转移、细胞生长和侵袭，然而，其在抗肿瘤药物化疗敏感性中的作用尚不清楚。在本研究中，我们分析了TCGA队列，发现WBSCR22在人类结直肠癌（CRC）组织中的表达显著升高。WBSCR22可作为总生存期（OS）的独立风险预测指标，WBSCR22上调可预测CRC患者的不良OS。敲低WBSCR22在体外和体内均显著增强CRC细胞对奥沙利铂的敏感性，而WBSCR22过表达导致细胞对奥沙利铂治疗产生耐药性。虽然敲低WBSCR22没有改变细胞周期，但增加了奥沙利铂诱导的细胞凋亡。敲低WBSCR22增强了奥沙利铂诱导的细胞内活性氧（ROS）生成以及ROS诱导的8-氧鸟嘌呤（8-oxoG）氧化损伤积累，可能使奥沙利铂治疗敏感化。这些结果表明，WBSCR22参与了CRC对奥沙利铂的耐药性，提示WBSCR22可能是一种新的奥沙利铂耐药生物标志物以及CRC治疗的潜在靶点。
