Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA

被引：899

作者：

Qu, Le ^{[1
]}

Ding, Jin ^{[2
]}

Chen, Cheng ^{[2
,3
]}

Wu, Zhen-Jie ^{[1
]}

Liu, Bing ^{[1
]}

Gao, Yi ^{[1
]}

Chen, Wei ^{[1
]}

Liu, Feng ^{[4
]}

Sun, Wen ^{[2
]}

Li, Xiao-Feng ^{[2
]}

Wang, Xue ^{[2
]}

Wang, Yue ^{[5
]}

Xu, Zhen-Yu ^{[5
]}

Gao, Li ^{[6
]}

Yang, Qing ^{[7
]}

Xu, Bin ^{[7
]}

Li, Yao-Ming ^{[7
]}

Fang, Zi-Yu ^{[7
]}

Xu, Zhi-Peng ^{[1
]}

Bao, Yi ^{[1
]}

Wu, Deng-Shuang ^{[1
]}

Miao, Xiong ^{[8
]}

Sun, Hai-Yang ^{[9
]}

Sun, Ying-Hao

Wang, Hong-Yang ^{[2
]}

Wang, Lin-Hui ^{[1
]}

机构：

[1] Second Mil Med Univ, Changzheng Hosp, Dept Urol, Shanghai 200003, Peoples R China

[2] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Int Cooperat Lab Signal Transduct, Shanghai 200003, Peoples R China

[3] Nanjing Univ, Sch Clin Med, Jinling Hosp, Dept Med Oncol, Nanjing 210002, Peoples R China

[4] Second Mil Med Univ, Coll Basic Med, Dept Med Genet, Shanghai 200433, Peoples R China

[5] Second Mil Med Univ, Coll Basic Med, Dept Histol & Embryol, Shanghai 200433, Peoples R China

[6] Second Mil Med Univ, Changhai Hosp, Dept Pathol, Shanghai 200433, Peoples R China

[7] Second Mil Med Univ, Changhai Hosp, Dept Urol, Shanghai 200433, Peoples R China

[8] Second Mil Med Univ, Changhai Hosp, Dept Orthoped, Shanghai 200433, Peoples R China

[9] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Orthoped, Hangzhou 310009, Zhejiang, Peoples R China

来源：

CANCER CELL | 2016年 / 29卷 / 05期

基金：

中国国家自然科学基金;

关键词：

NONCODING RNA; MICRORNA BIOGENESIS; CELLS; THERAPY; MIRNAS;

D O I：

10.1016/j.ccell.2016.03.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Sunitinib resistance is a major challenge for advanced renal cell carcinoma (RCC). Understanding the underlying mechanisms and developing effective strategies against sunitinib resistance are highly desired in the clinic. Here we identified an lncRNA, named lncARSR (lncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response. Therefore, lncARSR may serve as a predictor and a potential therapeutic target for sunitinib resistance.

引用

页码：653 / 668

页数：16

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