The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling

Mol Cancer. 2017 Jan 13;16(1):9. doi: 10.1186/s12943-017-0583-1.


Background: With more than 600,000 mortalities each year, colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. Recently, mechanisms involving noncoding RNAs have been implicated in the development of CRC.

Methods: We examined expression levels of lncRNA CRNDE and miR-181a-5p in 64 cases of CRC tissues and cell lines by qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of CRNDE and miR-181a-5p on proliferation and chemoresistance of CRC cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of CRNDE in CRC cells.

Results: In this study, we found that the expression levels of the CRNDE were upregulated in CRC clinical tissue samples. We identified microRNA miR-181a-5p as an inhibitory target of CRNDE. Both CRNDE knockdown and miR-181a-5p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that β-catenin and TCF4 were inhibitory targets of miR-181a-5p, and that Wnt/β-catenin signaling was inhibited by both CRNDE knockdown and miR-181a-5p overexpression. Significantly, we found that the repression of cell proliferation, the reduction of chemoresistance, and the inhibition of Wnt/β-catenin signaling induced by CRNDE knockdown would require the increased expression of miR-181a-5p.

Conclusions: Our study demonstrated that the lncRNA CRNDE could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-181a-5p and the activity of Wnt/β-catenin signaling.

Keywords: CRNDE; Chemoresistance; Colorectal cancer; Proliferation; Wnt/β-catenin signaling; miR-181a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Models, Biological
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • Transcription Factor 4
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Burden
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CRNDE RNA, human
  • MIRN-181 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors
  • beta Catenin