Linc00173 promotes chemoresistance and progression of small cell lung cancer by sponging miR-218 to regulate Etk expression
Linc00173 promotes chemoresistance and progression of small cell lung cancer by sponging miR-218 to regulate Etk expression
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Linc00173通过海绵miR-218调节Etk表达促进小细胞肺癌的化疗耐药和进展
DOI：
10.1038/s41388-019-0984-2
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发表时间：
2020-01-01
期刊：
影响因子：
8
通讯作者：
Guo, Linlang
中科院分区：
文献类型：
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作者：
Zeng, Fanrui;Wang, Qiongyao;Guo, Linlang
长链非编码RNA（lncRNAs）在癌症中的功能作用已得到广泛认可。然而，关于小细胞肺癌（SCLC）相关lncRNAs的研究却很少。在此，长基因间非蛋白编码RNA 173（Linc00173）首次被证明参与小细胞肺癌的化疗耐药和进展。我们发现Linc00173在小细胞肺癌耐药细胞系中高表达，并促进小细胞肺癌细胞的化疗耐药、增殖以及迁移侵袭。动物研究证实Linc00173在体内诱导小细胞肺癌的肿瘤化疗耐药和生长。此外，Linc00173通过“吸附”miRNA - 218作为一种竞争性内源RNA（ceRNA）而上调Etk，并导致GSKIP和NDRG1上调，从而引起β - 连环蛋白的易位。重要的是，表达分析显示Linc00173和Etk在小细胞肺癌患者样本中均上调，且呈现出Linc00173/Etk正相关。Linc00173的高表达与小细胞肺癌患者的化疗耐药、广泛期以及较短的生存期密切相关。总之，我们的研究阐明了一个由Linc00173介导的促进小细胞肺癌化疗耐药和进展的过程，这可能为小细胞肺癌的治疗策略提供依据。
The functional effects of long noncoding RNAs (lncRNAs) in cancer have been widely recognized. However, there is little research on SCLC-related lncRNAs. Here, long intergenic nonprotein coding RNA 173 (Linc00173) was first shown to be involved in chemoresistance and progression of small-cell lung cancer (SCLC). We found that Linc00173 was highly expressed in SCLC chemoresistant cell lines, and promoted SCLC cells chemoresistance, proliferation, and migration-invasion. Animal studies validated that Linc00173 induced tumor chemoresistance and growth of SCLC in vivo. Moreover, Linc00173 upregulated Etk through functioning as a competitive endogenous RNA (ceRNA) by “sponging” miRNA-218 and led to the upregulation of GSKIP and NDRG1, resulting in the translocation of β-catenin. Importantly, expression analysis revealed that both Linc00173 and Etk were upregulated in SCLC patient samples and exhibiting positive Linc00173/Etk correlation. High expression of Linc00173 closely correlated with chemoresistance, extensive stage, and shorter survival in SCLC patients. Collectively, our study illustrated a Linc00173-mediated process that facilitated chemoresistance and progression in SCLC, which might provide treatment strategy against SCLC.