MicroRNA-155 promotes the proliferation and invasion abilities of colon cancer cells by targeting quaking

Mol Med Rep. 2015 Mar;11(3):2355-9. doi: 10.3892/mmr.2014.2994. Epub 2014 Nov 21.

Abstract

The increasing expression of microRNA‑155 (miR‑155) and decreasing expression of RNA‑binding protein quaking (QKI) in colon cells have been observed previously. In this study, we attempted to establish the correlation between miR‑155 and QKI. In addition, we assessed whether the expression of miR‑155 and QKI is linked to the proliferation and invasion capabilities of colon cells. Firstly, nineteen tumor samples, divided into two groups according to the presence or absence of lymphatic metastasis, were obtained from colon cancer patients at the First Affiliated Hospital of Wenzhou Medical University, China. The expression level of miR‑155 and QKI was measured by quantitative polymerase chain reaction (qPCR). Secondly, the GES‑1, SW480 and COLO205 cell lines were cultured and the expression level of QKI and miR‑155 was also assessed by qPCR. Thirdly, a luciferase reporter gene assay was performed to detect the association between miR‑155 and QKI, and qPCR and western blot analysis were performed to confirm the effects of miR‑155 on the expression of QKI at the mRNA and protein level. Subsequently, the SW480 cells were used in the following experiments. Following treatment with miR‑155 inhibitor and QKI overexpression vector, western blot analysis, propidium iodide (PI) staining and a cell scratch assay were carried out to assess the effects of miR‑155 on the proliferation and invasion potential of colon cancer cells. qPCR findings revealed higher miR‑155 expression and lower QKI expression in colon cancer tissues as well as the colon cancer cell lines SW480 and COLO205. The relative luciferase activity of the 3' untranslated region (3'UTR) was decreased by approximately 45% when SW480 cells stimulated by mimic‑miR‑155 were combined with the wild‑type 3'UTR constructs. In addition, when the cells were treated with mimic‑miR‑155, QKI expression was significantly decreased at the mRNA and protein level. These outcomes revealed that miR‑155 decreased the production of QKI by acting on the 3'UTR of the QKI gene. Furthermore, PI staining and the cell scratch assay revealed that miR‑155 influenced the cell cycle and invasion abilities of colon cancer cells by directly targeting QKI and decreased the production of QKI by acting on the 3'UTR of the QKI gene. This study has demonstrated the correlation between miR‑155 and QKI, in which miR‑155 regulates the cell cycle and invasion ability of colon cancer cells via the modulation of QKI expression. Our study provides novel therapeutic strategies for colon cancer therapy.

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Binding Sites
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Gene Expression
  • Humans
  • Lactase / genetics
  • Lactase / metabolism
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA Interference*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism

Substances

  • 3' Untranslated Regions
  • Cadherins
  • MIRN155 microRNA, human
  • MicroRNAs
  • QKI protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Lactase