TY - JOUR
T1 - MicroRNAs induce epigenetic reprogramming and suppress malignant phenotypes of human colon cancer cells
AU - Ogawa, Hisataka
AU - Wu, Xin
AU - Kawamoto, Koichi
AU - Nishida, Naohiro
AU - Konno, Masamitsu
AU - Koseki, Jun
AU - Matsui, Hidetoshi
AU - Noguchi, Kozou
AU - Gotoh, Noriko
AU - Yamamoto, Tsuyoshi
AU - Miyata, Kanjiro
AU - Nishiyama, Nobuhiro
AU - Nagano, Hiroaki
AU - Yamamoto, Hirofumi
AU - Obika, Satoshi
AU - Kataoka, Kazunori
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
N1 - Publisher Copyright:
© 2015 Ogawa et al.
PY - 2015/5/13
Y1 - 2015/5/13
N2 - Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies have shown that reprogramming of colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy. Therefore, cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. It was also reported that the introduction of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR) 302s and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs are smaller than the genes of transcription factors, making them possibly suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell proliferation and invasion and the stimulation of the mesenchymal-to-epithelial transition phenotype in colon cancer cells. Importantly, the introduction of the ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and histone modification events. Furthermore, in vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis, which involves the mitochondrial Bcl2 protein family. The present study shows that the introduction of miR-302s and miR-369s could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors.
AB - Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies have shown that reprogramming of colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy. Therefore, cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. It was also reported that the introduction of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR) 302s and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs are smaller than the genes of transcription factors, making them possibly suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell proliferation and invasion and the stimulation of the mesenchymal-to-epithelial transition phenotype in colon cancer cells. Importantly, the introduction of the ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and histone modification events. Furthermore, in vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis, which involves the mitochondrial Bcl2 protein family. The present study shows that the introduction of miR-302s and miR-369s could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors.
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U2 - 10.1371/journal.pone.0127119
DO - 10.1371/journal.pone.0127119
M3 - Article
C2 - 25970424
AN - SCOPUS:84929301947
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e0127119
ER -