Hypoxia-induced lncHILAR promotes renal cancer metastasis via ceRNA for the miR-613/206/1-1-3p/Jagged-1/Notch/CXCR4 signaling pathway
Hypoxia-induced lncHILAR promotes renal cancer metastasis via ceRNA for the miR-613/206/1-1-3p/Jagged-1/Notch/CXCR4 signaling pathway
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DOI：
10.1016/j.ymthe.2021.05.020
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发表时间：
2021-10-06
影响因子：
12.4
通讯作者：
Zhai, Wei
中科院分区：
文献类型：
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作者：
Hu, Guanghui;Ma, Junjie;Zhai, Wei
缺氧已被确定为肿瘤进展（包括侵袭和转移）的常见因素。然而，缺氧条件下增强侵袭和转移的潜在机制仍不清楚。缺氧微环境通过上调LOC100506178的表达促进肾细胞癌（RCC）的侵袭和转移，我们将其命名为缺氧诱导的与RCC相关的长非编码RNA（lncRNA）（lncHILAR）。 lncHILAR的敲低抑制细胞侵袭和迁移，而lncHILAR的过表达则相反促进RCC细胞的细胞侵袭和迁移。值得注意的是，缺氧的 RCC 细胞分泌出包装有 lncHILAR 的外泌体，这些外泌体被常氧的 RCC 细胞摄取，然后驱动常氧的细胞侵袭。从机制上讲，lncHILAR 通过充当 miR-613/206/1-1-3p 的竞争性内源 RNA (ceRNA) 来增加 RCC 侵袭和转移，从而导致 Jagged-1 和 C-X-C 基序趋化因子受体 4 (CXCR4) 的上调。 Jagged-1/Notch/CXCR4 轴的激活诱导 RCC 转移。 lncHILAR 通过 miR-613/206/1-1-3p/Jagged-1/Notch/CXCR4 轴的 ceRNA 促进肾细胞癌细胞侵袭和转移。因此，新型 lncHILAR 可能作为 RCC 的潜在生物标志物和治疗靶点。
Hypoxia has been identified as a common contributor to tumor progression, including invasion and metastasis. However, the underlying mechanisms of enhanced invasion and metastasis under hypoxia remain unclear. A hypoxic microenvironment promotes invasion and metastasis of renal cell carcinoma (RCC) by upregulating expression of LOC100506178, which we named hypoxia-induced long non-coding RNA (lncRNA) associated with RCC (lncHILAR). Knockdown of lncHILAR inhibited cell invasion and migration, whereas overexpression of lncHILAR, conversely, facilitated cell invasion and migration of RCC cells. Notably, hypoxic RCC cells secreted exosomes packaged with lncHILAR, which were taken up by normoxic RCC cells and then drove normoxic cell invasion. Mechanistically, lncHILAR elevated RCC invasion and metastasis by acting as a competing endogenous RNA (ceRNA) for miR-613/206/1-1-3p, which led to the upregulation of Jagged-1 and the C-X-C motif chemokine receptor 4 (CXCR4). Activation of the Jagged-1/Notch/CXCR4 axis induced RCC metastasis. lncHILAR promotes RCC cell invasion and metastasis via ceRNA for the miR-613/206/1-1-3p/Jagged-1/Notch/CXCR4 axis. The novel lncHILAR may thus serve as a potential biomarker and therapeutic target in RCC.