Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA
Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA
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外泌体传输的 lncARSR 通过充当竞争性内源性 RNA 促进肾癌舒尼替尼耐药
DOI：
10.1016/j.ccell.2016.03.004
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发表时间：
2016-05-09
期刊：
影响因子：
50.3
通讯作者：
Wang, Lin-Hui
中科院分区：
文献类型：
--
作者：
Qu, Le;Ding, Jin;Wang, Lin-Hui
舒尼替尼耐药是晚期肾细胞癌（RCC）的主要挑战。了解舒尼替尼耐药的潜在机制并制定有效的策略是临床上非常需要的。在此我们鉴定了一种lncRNA，命名为lncARSR（在舒尼替尼耐药的RCC中lncRNA激活），其与临床上较差的舒尼替尼应答相关。lncARSR通过竞争性结合miR-34/miR-449促进RCC细胞中AXL和c-MET的表达来促进舒尼替尼耐药性。此外，具有生物活性的lncARSR可掺入外泌体并传递至敏感细胞，从而传播舒尼替尼耐药。用靶向lncARSR或AXL/c-MET抑制剂的锁核酸治疗舒尼替尼耐药RCC恢复了舒尼替尼反应。因此，lncARSR可作为舒尼替尼耐药的预测因子和潜在的治疗靶点。
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.