Effects of LDOC1 on colorectal cancer cells via downregulation of the Wnt/β-catenin signaling pathway

Oncol Rep. 2019 Jun;41(6):3281-3291. doi: 10.3892/or.2019.7126. Epub 2019 Apr 17.

Abstract

Colorectal cancer (CRC) is one of the most common tumor types of the digestive tract. Its incidence and mortality rates are among the highest of all gastrointestinal tumor types. The expression of leucine zipper downregulated in cancer 1 (LDOC1) is decreased in numerous cancer types. In the present study, the aim was to investigate the role of LDOC1 and determine the potential molecular mechanisms of its action in CRC. The expression of LDOC1 in CRC tissues and adjacent normal tissues was detected by reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry. LDOC1 expression in four CRC cell lines, compared with normal colorectal tissue, was determined by reverse transcription‑ polymerase chain reaction (RT‑PCR), and two cell lines with relatively low expression were screened. Human LDOC1 cDNA was inserted into a lentiviral vector, and transfected into HCT‑116 and Caco2 cell lines. The transfection efficiency was identified by RT‑PCR and western blot analysis. Cell proliferation was detected by Cell Counting Kit‑8 and colony formation assays. Cell cycle and apoptosis were detected by flow cytometry assay. Migration and invasion were assessed using Transwell and Matrigel assays, respectively. Additionally, whether LDOC1 regulates the Wnt/β‑catenin pathway was investigated by western blot analysis, and the expression and localization of β‑catenin in CRC cells were demonstrated by cellular immunofluorescence. LDOC1 expression was downregulated in CRC tissues and cells. LDOC1 overexpression inhibited cell proliferation, migration and invasion, but promoted cells apoptosis. Furthermore, LDOC1 downregulated the Wnt/β‑catenin pathway in CRC. In conclusion, LDOC1 is a tumor suppressor in CRC and it inhibits cell proliferation and promotes cell apoptosis. Additionally, it inhibits CRC cell metastasis by downregulating the Wnt/β‑catenin signaling pathway.

MeSH terms

  • Apoptosis / genetics
  • Caco-2 Cells
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • Transfection
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics*
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics

Substances

  • CTNNB1 protein, human
  • LDOC1 protein, human
  • Nuclear Proteins
  • Tumor Suppressor Proteins
  • beta Catenin