Interplay of long non-coding RNAs and HIF-1α: A new dimension to understanding hypoxia-regulated tumor growth and metastasis

Cancer Lett. 2021 Feb 28:499:49-59. doi: 10.1016/j.canlet.2020.11.007. Epub 2020 Nov 18.

Abstract

Hypoxia is a feature of the solid tumor microenvironment that is associated with poor clinical outcomes in multiple tumor types. Hypoxia-induced factor-1 alpha (HIF-1α) is a master regulator of hypoxic adaption, has been demonstrated to modulate hypoxic gene expression profiling and signaling transduction networks, and is thus a potential therapeutic target. Despite hypoxic response signaling having being extensively studied, the involvement of long non-coding RNAs (lncRNAs) in the hypoxic response has become a new focus of attention. Emerging evidence has documented complex interactions between HIF-1α and lncRNAs, which contribute to the acquisition of multiple hallmarks of cancer. In this review, we focus on recent advances in the study of hypoxia and HIF-1α-regulated lncRNAs, and summarize the molecular mechanisms and functional outcomes of the interplay between lncRNAs and HIF-1α, which may provide important insights into cancer diagnosis and prognosis, enabling better control of cancer.

Keywords: HIF-1α; Hallmarks of cancer; Hypoxia; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / genetics
  • Feedback, Physiological
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Protein Stability
  • RNA Stability
  • RNA, Long Noncoding / analysis
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Tumor Hypoxia / drug effects
  • Tumor Hypoxia / genetics
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Long Noncoding
  • RNA, Messenger