HOXA13 contributes to gastric carcinogenesis through DHRS2 interacting with MDM2 and confers 5-FU resistance by a p53-dependent pathway

被引:42
作者
Han, Yang [1 ]
Song, Chenlong [1 ]
Wang, Jianying [2 ]
Tang, Huamei [2 ]
Peng, Zhihai [1 ]
Lu, Su [2 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gen Surg, 100 Haining Rd, Shanghai 20080, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Pathol, 100 Haining Rd, Shanghai 20080, Peoples R China
基金
中国国家自然科学基金;
关键词
chemoresistance; DHRS2; gastric cancer; HOXA13; p53; MULTIDRUG-RESISTANCE; GENE-EXPRESSION; PROTEIN MRP1; TARGET GENES; CANCER; P53; CHEMOTHERAPY; OVEREXPRESSION; INCREASES; PROMOTES;
D O I
10.1002/mc.22793
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
5-FU-based chemotherapy is recently most recommended as the first-line treatment for gastric cancer (GC). However, 5-FU resistance is common for many postoperative GC patients. Homeobox A13 (HOXA13) is a member of homeobox genes highly expressed in many human tumors. Its potential roles and mechanisms of resistance to 5-FU in GC are poorly understood. In this study, we discovered that HOXA13 played an oncogenic role in vivo and in vitro. The patients with HOXA13 overexpression were closely related with poor prognosis and more prone to be resistant to 5-FU. Moreover, dehydrogenase/reductase 2 (DHRS2) was identified as a downstream gene of HOXA13. HOXA13 played a role of carcinogenesis through directly down-regulating DHRS2 to increase MDM2. Furthermore, HOXA13 conferred 5-FU resistance through MRP1 by a p53-dependent pathway. Therefore, HOXA13 might serve as a potential signature that recognized patients who were insensitive to 5-FU, and timely recommended them to other chemotherapy regimens.
引用
收藏
页码:722 / 734
页数:13
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