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 language | English |
|---|---|
| Pages (from-to) | 678-684 |
| Number of pages | 7 |
| Journal | Cancer Science |
| Volume | 108 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2017 Apr 1 |
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Keywords
- Intestinal tumor
- microRNA
- miR-194
- miR-215
- organoid
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Cluster microRNAs miR-194 and miR-215 suppress the tumorigenicity of intestinal tumor organoids. / Nakaoka, Toshiaki; Saito, Yoshimasa; Shimamoto, Yuriko; Muramatsu, Toshihide; Kimura, Masaki; Kanai, Yae; Saito, Hidetsugu.
In: Cancer Science, Vol. 108, No. 4, 01.04.2017, p. 678-684.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cluster microRNAs miR-194 and miR-215 suppress the tumorigenicity of intestinal tumor organoids
AU - Nakaoka, Toshiaki
AU - Saito, Yoshimasa
AU - Shimamoto, Yuriko
AU - Muramatsu, Toshihide
AU - Kimura, Masaki
AU - Kanai, Yae
AU - Saito, Hidetsugu
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
KW - Intestinal tumor
KW - microRNA
KW - miR-194
KW - miR-215
KW - organoid
UR - http://www.scopus.com/inward/record.url?scp=85018562648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018562648&partnerID=8YFLogxK
U2 - 10.1111/cas.13165
DO - 10.1111/cas.13165
M3 - Article
VL - 108
SP - 678
EP - 684
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 4
ER -