Functional role of long non-coding RNA CASC19/miR-140-5p/CEMIP axis in colorectal cancer progression in vitro

World J Gastroenterol. 2019 Apr 14;25(14):1697-1714. doi: 10.3748/wjg.v25.i14.1697.

Abstract

Background: Long non-coding RNAs (lncRNAs) are widely involved in tumor regulation. Nevertheless, the role of the lncRNA cancer susceptibility 19 (CASC19) in colorectal cancer (CRC) has yet to be fully clarified.

Aim: To explore the effect of CASC19 on proliferation and metastasizing ability of CRC cells.

Methods: CASC19 expression in human CRC tissues, pair-matched adjacent normal colon tissues, and CRC cells was detected using quantitative real-time PCR (qRT-PCR). CASC19 expression, as well as its relation to overall survival, was extrapolated by Kaplan-Meier survival analysis together with multivariable Cox regression assay. In vitro experiments were performed to confirm whether CASC19 regulates CRC cell invasion, migration, proliferation, and apoptosis.

Results: CASC19 expression was markedly upregulated in CRC tissues and CRC cell lines (P < 0.05). qRT-PCR revealed that CASC19 expression was higher in 25 tissue samples from patients with aggressive CRC compared with the 27 tissue samples from patients with nonaggressive CRC (P < 0.05). Higher CASC19 expression was associated with poorer patient prognoses. Furthermore, in vitro experiments demonstrated that CASC19 overexpression enhanced CRC cell invasion, migration, and proliferation. CASC19 overexpression enhanced the expression of cell migration inducing hyaluronidase 1 (CEMIP) and epithelial-mesenchymal transition markers. MiR-140-5p was found to be able to bind directly to CASC19 and CEMIP. Overexpression of miR-140-5p reversed the effect of CASC19 on cell proliferation and tumor migration, as well as suppressed CASC19-induced CEMIP expression.

Conclusion: CASC19 positively regulates CEMIP expression through targeting miR-140-5p. CASC19 may possess an oncogenic function in CRC progression, highlighting its potential as an essential biomarker in CRC diagnosis and therapy.

Keywords: Colorectal cancer; Long non-coding RNA; Metastasis; MicroRNA; Proliferation.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colon / pathology
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hyaluronoglucosaminidase
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation

Substances

  • MicroRNAs
  • Mirn140 microRNA, human
  • Proteins
  • RNA, Long Noncoding
  • CEMIP protein, human
  • Hyaluronoglucosaminidase