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
Article number15874
JournalNature Communications
Volume8
DOIs
Publication statusPublished - Jun 22 2017

Fingerprint

Long Noncoding RNA
Mouth Neoplasms
progressions
hypoxia
cancer
RNA
prognosis
genes
Carcinoma
Gene Regulatory Networks
signatures
activation
Transcriptional Activation
Names
shift
Neoplasms
Genes
predictions
Chemical activation
Hypoxia

ASJC Scopus subject areas

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

Cite this

Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression. / Shih, Jing Wen; Chiang, Wei Fan; Wu, Alexander T.H.; Wu, Ming Heng; Wang, Ling Yu; Yu, Yen Ling; Hung, Yu Wen; Wang, Wen Chang; Chu, Cheng Ying; Hung, Chiu Lien; Changou, Chun A.; Yen, Yun; Kung, Hsing Jien.

In: Nature Communications, Vol. 8, 15874, 22.06.2017.

Research output: Contribution to journalArticle

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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.",
author = "Shih, {Jing Wen} and Chiang, {Wei Fan} and Wu, {Alexander T.H.} and Wu, {Ming Heng} and Wang, {Ling Yu} and Yu, {Yen Ling} and Hung, {Yu Wen} and Wang, {Wen Chang} and Chu, {Cheng Ying} and Hung, {Chiu Lien} and Changou, {Chun A.} and Yun Yen and Kung, {Hsing Jien}",
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T1 - Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression

AU - Shih, Jing Wen

AU - Chiang, Wei Fan

AU - Wu, Alexander T.H.

AU - Wu, Ming Heng

AU - Wang, Ling Yu

AU - Yu, Yen Ling

AU - Hung, Yu Wen

AU - Wang, Wen Chang

AU - Chu, Cheng Ying

AU - Hung, Chiu Lien

AU - Changou, Chun A.

AU - Yen, Yun

AU - Kung, Hsing Jien

PY - 2017/6/22

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N2 - 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.

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