miR-21 and its target gene CCL20 are both highly overexpressed in the microenvironment of colorectal tumors: significance of their regulation

Oncol Rep. 2013 Sep;30(3):1285-92. doi: 10.3892/or.2013.2580. Epub 2013 Jul 1.


Recently, we reported a functional interaction between miR-21 and its identified chemokine target CCL20 in colorectal cancer (CRC) cell lines. Here, we investigated whether such functional interactions are permitted at the cellular level which would require an inverse correlation of expression and also co-expression of miR-21 and CCL20 in the same cell. Expression profiling was performed using qPCR, and ELISA, in situ hybridization and immunohistochemistry were applied for the presentation of their cellular localization. We demonstrated that miR-21 as well as CCL20 were both significantly upregulated in CRC tissues; thus, showing no antidromic expression pattern. This provided an initial clue that miR-21 and CCL20 may not be expressed in the same cell. In addition, we located miR-21 expression at the cellular level predominantly in stromal cells such as tumor-associated fibroblasts and to a minor degree in immune cells such as macrophages and lymphocytes. Likewise, CCL20 expression was primarily detected in tumor-infiltrating immune cells. Thus, investigating the cellular localization of miR-21 and its target CCL20 revealed that both molecules are expressed predominantly in the microenvironment of CRC tumors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Proliferation
  • Chemokine CCL20 / genetics
  • Chemokine CCL20 / metabolism*
  • Cohort Studies
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • Tumor Microenvironment*


  • CCL20 protein, human
  • Chemokine CCL20
  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Messenger