Long non-coding RNA and tumor hypoxia: New players ushered toward an old arena

Jing Wen Shih, Hsing-Jien Kung

Research output: Contribution to journalReview article

27 Scopus citations

Abstract

Hypoxia is a classic feature of the tumor microenvironment with a profound impact on cancer progression and therapeutic response. Activation of complex hypoxia pathways orchestrated by the transcription factor HIF (hypoxia-inducible factor) contributes to aggressive phenotypes and metastasis in numerous cancers. Over the past few decades, exponentially growing research indicated the importance of the non-coding genome in hypoxic tumor regions. Recently, key roles of long non coding RNAs (lncRNAs) in hypoxia-driven cancer progression have begun to emerge. These hypoxia-responsive lncRNAs (HRLs) play pivotal roles in regulating hypoxic gene expression at chromatic, transcriptional, and post-transcriptional levels by acting as effectors of the indirect response to HIF or direct modulators of the HIF-transcriptional cascade. Notably, the aberrant expression of HRLs significantly correlates with poor outcomes in cancer patients, showing promise for future utility as a tumor marker or therapeutic target. Here we address the latest advances made toward understanding the functional relevance of HRLs, the involvement of these transcripts in hypoxia response and the underlying action mechanisms, highlighting their specific roles in HIF-1 signaling regulation and hypoxia-associated malignant transformation.

Original languageEnglish (US)
Article number53
JournalJournal of Biomedical Science
Volume24
Issue number1
DOIs
StatePublished - Aug 8 2017

Keywords

  • Cancer
  • HIF-1α
  • HRL
  • Hypoxia
  • Hypoxia-responsive lncRNAs
  • lncRNA
  • Long non-coding RNA
  • Metastasis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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