miR-301a plays a pivotal role in hypoxia-induced gemcitabine resistance in pancreatic cancer

被引：26
作者：
Luo, Guangtao [1 ]
Xia, Xiang [2 ]
Wang, Xiaofeng [1 ]
Zhang, Kundong [1 ]
Cao, Jun [1 ]
Jiang, Tao [1 ]
Zhao, Qian [3 ,4 ]
Qiu, Zhengjun [1 ]
机构：
[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gen Surg, 100 Haining Rd, Shanghai 200080, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Renji Hosp, Dept Gen Surg, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis, Dept Pathophysiol, 280 South Chongqing Rd, Shanghai 200025, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Natl Minist Educ, 280 South Chongqing Rd, Shanghai 200025, Peoples R China
来源：
EXPERIMENTAL CELL RESEARCH | 2018年 / 369卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Gemcitabine resistance; Hypoxia; MiR-301a; Pancreatic cancer; TAp63; CELL-PROLIFERATION; TAP63; METASTASIS; DEGRADATION; EXPRESSION; MICRORNAS; APOPTOSIS; INVASION;
D O I：
10.1016/j.yexcr.2018.05.013
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Hypoxia is a hallmark of pancreatic cancer (PC) and is associated with gemcitabine resistance. However, the mechanisms underlying hypoxia-induced gemcitabine resistance in PC remain greatly unknown. Our previous work showed that miR-301a, a hypoxia-sensitive miRNA, is involved in PC metastasis under hypoxia via regulation of its target gene P63. Here, we showed that miR-301a was upregulated in a NF-kappa B independent manner and promoted gemcitabine resistance under hypoxic conditions in vitro. In addition, TAp63, a member of the P63 family, reversed hypoxia-induced gemcitabine resistance by promoting degradation of HIF-1 alpha. Furthermore, we proved that TAp63 was a functional downstream target of miR-301a and mediated the biological properties of miR-301a in PC. Taken together, these findings indicate that miR-301a exerts as a critical regulator involved in hypoxia-induced gemcitabine resistance in PC and may have potentials to be a therapeutic target for PC patients.
引用
收藏
页码：120 / 128
页数：9
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