Cluster microRNAs miR-194 and miR-215 suppress the tumorigenicity of intestinal tumor organoids

Toshiaki Nakaoka, Yoshimasa Saito, Yuriko Shimamoto, Toshihide Muramatsu, Masaki Kimura, Yae Kanai, Hidetsugu Saito

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Tumor stem cells with self-renewal and multipotent capacity play critical roles in the initiation and progression of cancer. Recently, a new 3-D culture system known as organoid culture has been developed, allowing Lgr5-positive stem cells to form organoids that resemble the properties of original tissues. Here we established organoids derived from intestinal tumors of Apcmin/+ mice and normal intestinal epithelia of C57BL/6J mice and investigated the roles of microRNA (miRNA) in intestinal tumor organoids. The results of microarray analyses revealed that expression of the cluster miRNAs, miR-194 and miR-215 was markedly suppressed in intestinal tumor organoids in comparison with organoids derived from normal intestinal epithelia. Enforced expression of miR-194 resulted in inhibition of E2f3, a positive regulator of the cell cycle and growth suppression of intestinal tumor organoids. In addition, enforced expression of miR-215 suppressed the cancer stem cell signature through downregulation of intestinal stem cell markers including Lgr5. These findings indicate that the miRNA cluster including miR-194 and miR-215 plays important roles in suppressing the growth and attenuating the stemness of intestinal tumor organoids.

Original languageEnglish
Pages (from-to)678-684
Number of pages7
JournalCancer Science
Volume108
Issue number4
DOIs
Publication statusPublished - 2017 Apr 1

Keywords

  • Intestinal tumor
  • microRNA
  • miR-194
  • miR-215
  • organoid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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