HOTAIR regulates colorectal cancer stem cell properties and promotes tumorigenicity by sponging miR-211-5p and modulating FLT-1

Cell Cycle. 2021 Oct;20(19):1999-2009. doi: 10.1080/15384101.2021.1962636. Epub 2021 Sep 1.

Abstract

We intended to investigate the underlying mechanism of action of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in colorectal cancer (CRC) progression, especially in tumor cell stemness. For that purpose, different assays were performed such as real-time PCR and western blotting to determine the expression of target genes. Cell stemness was determined by sphere formation assay, flow cytometry assay, and the analysis of stemness-related markers. The interplay among target genes was evaluated using bioinformatics analyses, luciferase reporter and biotin-labeled RNA pull down assays. We found that HOTAIR was highly expressed and predicted poor prognosis survival in CRC. Downregulation of HOTAIR repressed tumor malignant behaviors and cancer stemness. Mechanistically, HOTAIR facilitated the expression of the microRNA (miR)-211-5p target gene fms-like tyrosine kinase-1 (FLT-1), thereby modulating cancer stem cell (CSC) properties in CRC. We conclude that HOTAIR/miR-211-5p/FLT-1 axis contributes to CRC cancer stemness.

Keywords: Colorectal cancer; FLT-1; HOTAIR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplastic Stem Cells / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Vascular Endothelial Growth Factor Receptor-1* / genetics
  • Vascular Endothelial Growth Factor Receptor-1* / metabolism

Substances

  • HOTAIR long untranslated RNA, human
  • MIRN211 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1

Grants and funding

This work was supported by Science and Technology Research Project of Liaoning Provincial Education Department (JYTJCZR2020059).