Detection of circulating microRNAs with Ago2 complexes to monitor the tumor dynamics of colorectal cancer patients during chemotherapy

Int J Cancer. 2019 May 1;144(9):2169-2180. doi: 10.1002/ijc.31960. Epub 2019 Jan 7.


Because of the different forms of circulating miRNAs in plasma, Argonaute2 (Ago2)-miRNAs and extracellular vesicles (EV-miRNAs), we examined the two forms of extracellular miRNAs in vitro and developed a unique methodology to detect circulating Ago2-miRNAs in small volumes of plasma. We demonstrated that Ago2-miR-21 could be released into the extracellular fluid by active export from viable cancer cells and cytolysis in vitro. As miR-21 and miR-200c were abundantly expressed in both metastatic liver sites and primary lesions, we evaluated Ago2-miR-21 as a candidate biomarker of both active export and cytolysis while Ago2-miR-200c as a biomarker of cytolysis in plasma obtained from colorectal cancer (CRC) patients before treatment and in a series of plasma obtained from CRC patients with liver metastasis who received systemic chemotherapy. The measurement of Ago2-miR-21 allowed us to distinguish CRC patients from subjects without CRC. The trend in ΔCt values for Ago2-miR-21 and -200c during chemotherapy could predict tumor response to ongoing treatment. Thus, capturing circulating Ago2-miRNAs from active export can screen patients with tumor burdens, while capturing them from passive release by cytolysis can monitor tumor dynamics during chemotherapy treatment.

Keywords: Ago2; chemotherapy; circulating miRNA; colorectal cancer; liquid biopsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / blood*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Circulating MicroRNA / analysis*
  • Circulating MicroRNA / metabolism
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Extracellular Vesicles / pathology
  • HT29 Cells
  • Humans
  • MicroRNAs / blood*


  • AGO2 protein, human
  • Argonaute Proteins
  • Biomarkers, Tumor
  • Circulating MicroRNA
  • MIRN200 microRNA, human
  • MIRN21 microRNA, human
  • MIRN3120 microRNA, human
  • MicroRNAs