Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA
Authors: Lin-Hui Wang
Yi Bao
Le Qu
Xiao-Feng Li
Wei Chen
Yue Wang
Wen Sun
Jin Ding
Xue Wang
Zi-Yu Fang
Qing Yang
Feng Liu
Zhen-Yu Xu
Cheng Chen
Bin Xu
Yao-Ming Li
Hai-Yang Sun
Zhen-Jie Wu
Yi Gao
Li Gao
Hong-Yang Wang
Ying-Hao Sun
Xiong Miao
Deng-Shuang Wu
Bing Liu
Zhi-Peng Xu
Journal: Cancer Cell (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Sunitinib resistance; lncARSR; miR-34; miR-449; AXL
Affiliations: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China., The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China., The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China; Department of Medical Oncology, Jinling Hospital, Nanjing University Clinical School of Medicine, Nanjing 210002, China., Department of Medical Genetics, College of Basic Medicine, Second Military Medical University, Shanghai 200433, China., Department of Histology and Embryology, College of Basic Medicine, Second Military Medical University, Shanghai 200433, China., Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China., The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: ., Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: .

Abstract:  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. 

Retracted: No

PubPeer comments:
 According to the title, the paper is supposed to address u201c**the finance achievements of transnational corporation**u201d. However, no related papers on this topic are included in the reference list. Basically, this paper is nothing to do with u201c**the finance achievements of transnational corporation**u201d. The only related part is an illustrative example in Section 6 as an imaginary application without any technical details. Besides, the proposed operators are not justified and are actually just symbol manipulation. For instance, the operator defined by eq.(13) does not work as a weighted version. ![file] ![file] ,