Long non-coding RNA HOTAIR is targeted and regulated by miR-141 in human cancer cells

J Biol Chem. 2014 May 2;289(18):12550-65. doi: 10.1074/jbc.M113.488593. Epub 2014 Mar 10.


HOTAIR is a long non-coding RNA that interacts with the polycomb repressive complex and suppresses its target genes. HOTAIR has also been demonstrated to promote malignancy. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition process, and the expression of miR-141 is inversely correlated with tumorigenicity and invasiveness in several human cancers. We found that HOTAIR expression is inversely correlated to miR-141 expression in renal carcinoma cells. HOTAIR promotes malignancy, including proliferation and invasion, whereas miR-141 suppresses malignancy in human cancer cells. miR-141 binds to HOTAIR in a sequence-specific manner and suppresses HOTAIR expression and functions, including proliferation and invasion. Both HOTAIR and miR-141 were associated with the immunoprecipitated Ago2 (Argonaute2) complex, and the Ago2 complex cleaved HOTAIR in the presence of miR-141. These results demonstrate that HOTAIR is suppressed by miR-141 in an Ago2-dependent manner.

Keywords: Cancer Biology; Cell Growth; Gene Regulation; Genistein; HOTAIR; Invasion; Long Non-coding RNA; MicroRNA; Renal Carcinoma; miR-141.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoptosis / genetics
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Base Sequence
  • Binding Sites / genetics
  • Blotting, Western
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic*
  • HT29 Cells
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mutation
  • Neoplasm Invasiveness
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc Finger E-box-Binding Homeobox 1


  • AGO2 protein, human
  • Argonaute Proteins
  • HOTAIR long untranslated RNA, human
  • Homeodomain Proteins
  • MIRN141 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1