Exosomes from CD133+ cells carrying circ-ABCC1 mediate cell stemness and metastasis in colorectal cancer

J Cell Biochem. 2020 Jun;121(5-6):3286-3297. doi: 10.1002/jcb.29600. Epub 2020 Jan 21.

Abstract

Colorectal cancer (CRC), a fatal tumor, has been diagnosed as one of the most prevalent types of cancers globally, inducing multiple cancer-linked deaths. Mounting evidence has revealed that circular RNA (circRNA) elicits a regulatory impact on the initiation and development of cancers. Emerged as a new circRNA, hsa_circ_0000677 (circ-ABCC1) has not been studied in cancer progression. This study is the first attempt to explore the regulatory role of circ-ABCC1 in CRC. In this study, data from sphere-forming, transwell, and Western blot analyses revealed that cell stemness, sphere formation, and metastasis were notably enhanced in CD133+ cells isolated from CRC cells. In addition, exosomes from CD133+ cells could promote cell stemness, sphere formation, and metastasis. Moreover, circ-ABCC1 was verified to be characterized with a loop structure through quantitative reverse-transcription polymerase chain reaction analysis. Functional assays testified that the upregulation of circ-ABCC1 contributed to cell stemness, sphere formation, and metastasis in CD133- /Caco2 or CD133- /HCT15 cells. Furthermore, the interaction between circ-ABCC1 and β-catenin was analyzed via RNA immunoprecipitation and RNA pull-down and finally, circ-ABCC1 was confirmed to facilitate CRC progression by activating the Wnt/β-catenin pathway. To sum up, exosomes from CD133+ cells carrying circ-ABCC1 can mediate cell stemness and metastasis in CRC, unveiling that circ-ABCC1 serves as a novel candidate target for CRC treatment.

Keywords: CRC; Wnt/β-catenin pathway; circ-ABCC1.

MeSH terms

  • AC133 Antigen / metabolism*
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colonic Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Exosomes / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / cytology
  • RNA, Circular / genetics*
  • Subcellular Fractions
  • Wnt Proteins / metabolism

Substances

  • AC133 Antigen
  • Multidrug Resistance-Associated Proteins
  • PROM1 protein, human
  • RNA, Circular
  • Wnt Proteins
  • multidrug resistance-associated protein 1