Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA
Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA
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长非编码 RNA LINC00336 通过作为竞争性内源 RNA 抑制肺癌铁死亡
DOI：
10.1038/s41418-019-0304-y
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发表时间：
2019-11-01
影响因子：
12.4
通讯作者：
Zhang, Bin
中科院分区：
文献类型：
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作者：
Wang, Min;Mao, Chao;Zhang, Bin
长链非编码rna （long noncoding rna, lncRNAs）和microRNAs之间的调控环在转录和翻译调控中具有动态作用，并与癌症有关。然而，lncrna和microrna之间的调控通路在肿瘤发生中的作用仍然是难以捉摸的。在这里，我们证明了核lncRNA LINC00336在肺癌中上调，并通过作为竞争内源性RNA （ceRNAs）作为致癌基因发挥作用。LINC00336利用LINC00336的核苷酸1901-2107、RRM相互作用域和ELAVL1的关键氨基酸（aa 101-213）结合rna结合蛋白ELAVL1 (elav样rna结合蛋白1)，抑制铁凋亡。此外，ELAVL1通过稳定其转录后水平增加了LINC00336的表达，而LSH（淋巴特异性解旋酶）通过p53信号通路增加了ELAVL1的表达，进一步支持了LSH促进LINC00336表达的假设。有趣的是，LINC00336作为microRNA 6852 （MIR6852）的内源性海绵，调节半胱硫氨酸-β-合成酶（CBS）的表达，CBS是铁死亡的替代标志物。最后，我们发现MIR6852通过促进铁下垂来抑制细胞生长。这些数据表明lncRNA和ceRNA网络在肿瘤发生和铁下垂中具有重要作用。
The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional and translational regulation, and is involved in cancer. However, the regulatory circuitry between lncRNAs and microRNAs in tumorigenesis remains elusive. Here we demonstrate that a nuclear lncRNA LINC00336 is upregulated in lung cancer and functions as an oncogene by acting as a competing endogenous RNA (ceRNAs). LINC00336 bound RNA-binding protein ELAVL1 (ELAV-like RNA-binding protein 1) using nucleotides 1901–2107 of LINC00336 and the RRM interaction domain and key amino acids (aa) of ELAVL1 (aa 101–213), inhibiting ferroptosis. Moreover, ELAVL1 increased LINC00336 expression by stabilizing its posttranscriptional level, whereas LSH (lymphoid-specific helicase) increased ELAVL1 expression through the p53 signaling pathway, further supporting the hypothesis that LSH promotes LINC00336 expression. Interestingly, LINC00336 served as an endogenous sponge of microRNA 6852 (MIR6852) to regulate the expression of cystathionine-β-synthase (CBS), a surrogate marker of ferroptosis. Finally, we found that MIR6852 inhibited cell growth by promoting ferroptosis. These data show that the network of lncRNA and ceRNA has an important role in tumorigenesis and ferroptosis.