Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression.
Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression.
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长链非编码RNA LncHIFCAR/MIR 31 HG是一种驱动口腔癌进展的HIF-1α共激活剂。
DOI：
10.1038/ncomms15874
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发表时间：
2017-06-22
影响因子：
16.6
通讯作者：
Kung HJ
中科院分区：
文献类型：
--
作者：
Shih JW;Chiang WF;Wu ATH;Wu MH;Wang LY;Yu YL;Hung YW;Wang WC;Chu CY;Hung CL;Changou CA;Yen Y;Kung HJ
Long noncoding RNAs (lncRNAs) have been implicated in hypoxia/HIF-1-associated cancer progression through largely unknown mechanisms. Here we identify MIR31HG as a hypoxia-inducible lncRNA and therefore we name it LncHIFCAR (long noncoding HIF-1α co-activating RNA); we describe its oncogenic role as a HIF-1α co-activator that regulates the HIF-1 transcriptional network, crucial for cancer development. Extensive analyses of clinical data indicate LncHIFCAR level is substantially upregulated in oral carcinoma, significantly associated with poor clinical outcomes and representing an independent prognostic predictor. Overexpression of LncHIFCAR induces pseudo-hypoxic gene signature, whereas knockdown of LncHIFCAR impairs the hypoxia-induced HIF-1α transactivation, sphere-forming ability, metabolic shift and metastatic potential in vitro and in vivo. Mechanistically, LncHIFCAR forms a complex with HIF-1α via direct binding and facilitates the recruitment of HIF-1α and p300 cofactor to the target promoters. Our results uncover an lncRNA-mediated mechanism for HIF-1 activation and establish the clinical values of LncHIFCAR in prognosis and potential therapeutic strategy for oral carcinoma. Cancer cells adapt to the changing microenvironment by activating different pathways through multiple mechanisms. Here the authors identify long noncoding RNA MIR31HG as a HIF-1α co-activator required for the induction of the hypoxic response and show its oncogenic role in oral carcinogenesis.
