LncRNA LINC00525 activates HIF-1α through miR-338-3p / UBE2Q1 / β-catenin axis to regulate the Warburg effect in colorectal cancer

Bioengineered. 2022 Feb;13(2):2554-2567. doi: 10.1080/21655979.2021.2018538.

Abstract

Warburg effect is considered to be related to the malignancy of tumor cells under hypoxic conditions, but the underlying mechanism remains unknown. In this article, it has been reported that lncRNA LINC00525 is a hypoxia-responsive lncRNA and is essential for hypoxia-enhanced glycolysis. It was found that LINC00525 was up-regulated, and promoted cell proliferation in colorectal cancer in vitro and in vivo. In colorectal cancer cells, hypoxia increasedLINC00525 expression, whereas knocking down LINC00525 reduced hypoxia-enhanced glycolysis. For specific molecular mechanisms, it was found that LINC00525 promoted UBE2Q1 expression by binding miR-338-3p, and UBE2Q1-stabilized β-catenin enhances hypoxia-enhanced glycolysis by activating HIF-1α. In conclusion, these findings showed that LINC00525 was essential for hypoxia-enhanced glycolysis; its mechanism was related to activating HIF-1α through miR-338-3p/UBE2Q1/β-catenin axis in colorectal cancer cells.

Keywords: Colorectal cancer; HIF-1α; LINC00525; Warburg effect; ubiquitination.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Humans
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN338 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • beta Catenin
  • UBE2Q1 protein, human
  • Ubiquitin-Conjugating Enzymes

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.