LncIHAT is induced by hypoxia-inducible factor 1 and promotes breast cancer progression

Lin Chen, Lei Bao, Yanling Niu, Jennifer E. Wang, Ashwani Kumar, Chao Xing, Yingfei Wang, Weibo Luo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Hypoxia induces thousands of mRNAs and miRNAs to mediate tumor malignancy. However, hypoxia-induced long noncoding RNA (lncRNA) transcriptome and their role in triple-negative breast cancer (TNBC) have not been defined. Here we identified hypoxia-induced lncRNA transcriptome in two human TNBC cell lines by whole transcriptome sequencing. AC093818.1 was one of 26 validated lncRNAs and abundantly expressed in TNBC in vitro and in vivo. 50- and 30-rapid amplification of cDNA ends assays revealed that the isoform 2 was a dominant AC093818.1 transcript in TNBC cells and thus referred to as lncIHAT (lncRNA induced by hypoxia and abundant in TNBC). Hypoxia-inducible factor 1 (HIF1) but not HIF2 bound to the hypoxia response element at the promoter of lncIHAT to activate its transcription in hypoxic TNBC cells. LncIHAT promoted TNBC cell survival in vitro and tumor growth and lung metastasis in mice. Mechanistically, lncIHAT was required for the expression of its proximal neighboring oncogenic genes PDK1 and ITGA6 in TNBC cells and tumors. Reexpression of PDK1 and ITGA6 rescued survival and growth of lncIHAT knockdown TNBC cells in vitro. Collectively, these findings uncovered lncIHAT as a new hypoxia-induced oncogenic cis-acting lncRNA in TNBC.

Original languageEnglish (US)
Pages (from-to)678-687
Number of pages10
JournalMolecular Cancer Research
Volume19
Issue number4
DOIs
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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