Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression

Jing Wen Shih, Wei Fan Chiang, Alexander T.H. Wu, Ming Heng Wu, Ling Yu Wang, Yen Ling Yu, Yu Wen Hung, Wen Chang Wang, Cheng Ying Chu, Chiu Lien Hung, Chun A. Changou, Yun Yen, Hsing-Jien Kung

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number15874
JournalNature Communications
Volume8
DOIs
StatePublished - Jun 22 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Shih, J. W., Chiang, W. F., Wu, A. T. H., Wu, M. H., Wang, L. Y., Yu, Y. L., Hung, Y. W., Wang, W. C., Chu, C. Y., Hung, C. L., Changou, C. A., Yen, Y., & Kung, H-J. (2017). Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression. Nature Communications, 8, [15874]. https://doi.org/10.1038/ncomms15874