A Cancer Reprogramming Method Using MicroRNAs as a Novel Therapeutic Approach against Colon Cancer: Research for Reprogramming of Cancer Cells by MicroRNAs

Susumu Miyazaki, Hirofumi Yamamoto, Norikatsu Miyoshi, Xin Wu, Hisataka Ogawa, Mamoru Uemura, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Masamitsu Konno, Yuichiro Doki, Masaki Mori, Hideshi Ishii

研究成果: ジャーナルへの寄稿記事

13 引用 (Scopus)

抄録

Background: We previously generated induced pluripotent stem cells by reprograming adipose stem cells through the introduction of microRNAs targeting four transcription factors (Oct3/4, Sox2, c-Myc, and Klf4). In this study, we aimed to reprogram cancer cells using microRNAs to explore their therapeutic potential. Methods: Mature microRNAs (mir-302a-d, 369-3p and 5p, and mir-200c, as needed) were introduced into colon cancer cells (DLD-1, RKO, and HCT116) using lipofection. Results: The transfected cells exhibited an embryonic stem cell-like morphology and expressed the undifferentiated marker genes Nanog, Oct3/4, SOX2, and Klf4, as well as tumor-related antigen-1-60. These cells expressed neurogenic or adipogenic markers, indicating that reprogramming of the cancer cells was partially successful. Moreover, we found that miRNA-expressing DLD-1 cells showed low proliferative activity in vitro and in vivo, accompanied by increased expression of the tumor suppressor genes p16ink4a and p21waf1. miRNA-expressing DLD-1 cells also exhibited enhanced sensitivity to 5-fluorouracil, possibly through the downregulation of multidrug-resistant protein 8. The reprogrammed cells from DLD-1, RKO, and HCT116 cells exhibited reduced c-Myc expression, in contrast to the high c-Myc expression in the induced pluripotent cancer cells that were generated using four transcription factors. Conclusions: Our cancer reprogramming method employing simple lipofection of mature microRNAs is safe and well suited for clinical application, because it avoids integration of exogenous genes into the host genome and allows escape from augmentation of c-Myc gene expression.

元の言語英語
ページ(範囲)1394-1401
ページ数8
ジャーナルAnnals of Surgical Oncology
22
DOI
出版物ステータス出版済み - 12 1 2015

Fingerprint

MicroRNAs
Colonic Neoplasms
Research
Neoplasms
Therapeutics
Transcription Factors
HCT116 Cells
Induced Pluripotent Stem Cells
myc Genes
Cellular Reprogramming
Neoplasm Antigens
Embryonic Stem Cells
Tumor Suppressor Genes
Fluorouracil
Genes
Stem Cells
Down-Regulation
Genome
Gene Expression
Proteins

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

これを引用

A Cancer Reprogramming Method Using MicroRNAs as a Novel Therapeutic Approach against Colon Cancer : Research for Reprogramming of Cancer Cells by MicroRNAs. / Miyazaki, Susumu; Yamamoto, Hirofumi; Miyoshi, Norikatsu; Wu, Xin; Ogawa, Hisataka; Uemura, Mamoru; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Konno, Masamitsu; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi.

:: Annals of Surgical Oncology, 巻 22, 01.12.2015, p. 1394-1401.

研究成果: ジャーナルへの寄稿記事

Miyazaki, S, Yamamoto, H, Miyoshi, N, Wu, X, Ogawa, H, Uemura, M, Nishimura, J, Hata, T, Takemasa, I, Mizushima, T, Konno, M, Doki, Y, Mori, M & Ishii, H 2015, 'A Cancer Reprogramming Method Using MicroRNAs as a Novel Therapeutic Approach against Colon Cancer: Research for Reprogramming of Cancer Cells by MicroRNAs', Annals of Surgical Oncology, 巻. 22, pp. 1394-1401. https://doi.org/10.1245/s10434-014-4217-1
Miyazaki, Susumu ; Yamamoto, Hirofumi ; Miyoshi, Norikatsu ; Wu, Xin ; Ogawa, Hisataka ; Uemura, Mamoru ; Nishimura, Junichi ; Hata, Taishi ; Takemasa, Ichiro ; Mizushima, Tsunekazu ; Konno, Masamitsu ; Doki, Yuichiro ; Mori, Masaki ; Ishii, Hideshi. / A Cancer Reprogramming Method Using MicroRNAs as a Novel Therapeutic Approach against Colon Cancer : Research for Reprogramming of Cancer Cells by MicroRNAs. :: Annals of Surgical Oncology. 2015 ; 巻 22. pp. 1394-1401.
@article{312b7bece53549f4b3b8432ee3cce178,
title = "A Cancer Reprogramming Method Using MicroRNAs as a Novel Therapeutic Approach against Colon Cancer: Research for Reprogramming of Cancer Cells by MicroRNAs",
abstract = "Background: We previously generated induced pluripotent stem cells by reprograming adipose stem cells through the introduction of microRNAs targeting four transcription factors (Oct3/4, Sox2, c-Myc, and Klf4). In this study, we aimed to reprogram cancer cells using microRNAs to explore their therapeutic potential. Methods: Mature microRNAs (mir-302a-d, 369-3p and 5p, and mir-200c, as needed) were introduced into colon cancer cells (DLD-1, RKO, and HCT116) using lipofection. Results: The transfected cells exhibited an embryonic stem cell-like morphology and expressed the undifferentiated marker genes Nanog, Oct3/4, SOX2, and Klf4, as well as tumor-related antigen-1-60. These cells expressed neurogenic or adipogenic markers, indicating that reprogramming of the cancer cells was partially successful. Moreover, we found that miRNA-expressing DLD-1 cells showed low proliferative activity in vitro and in vivo, accompanied by increased expression of the tumor suppressor genes p16ink4a and p21waf1. miRNA-expressing DLD-1 cells also exhibited enhanced sensitivity to 5-fluorouracil, possibly through the downregulation of multidrug-resistant protein 8. The reprogrammed cells from DLD-1, RKO, and HCT116 cells exhibited reduced c-Myc expression, in contrast to the high c-Myc expression in the induced pluripotent cancer cells that were generated using four transcription factors. Conclusions: Our cancer reprogramming method employing simple lipofection of mature microRNAs is safe and well suited for clinical application, because it avoids integration of exogenous genes into the host genome and allows escape from augmentation of c-Myc gene expression.",
author = "Susumu Miyazaki and Hirofumi Yamamoto and Norikatsu Miyoshi and Xin Wu and Hisataka Ogawa and Mamoru Uemura and Junichi Nishimura and Taishi Hata and Ichiro Takemasa and Tsunekazu Mizushima and Masamitsu Konno and Yuichiro Doki and Masaki Mori and Hideshi Ishii",
year = "2015",
month = "12",
day = "1",
doi = "10.1245/s10434-014-4217-1",
language = "English",
volume = "22",
pages = "1394--1401",
journal = "Annals of Surgical Oncology",
issn = "1068-9265",
publisher = "Springer New York",

}

TY - JOUR

T1 - A Cancer Reprogramming Method Using MicroRNAs as a Novel Therapeutic Approach against Colon Cancer

T2 - Research for Reprogramming of Cancer Cells by MicroRNAs

AU - Miyazaki, Susumu

AU - Yamamoto, Hirofumi

AU - Miyoshi, Norikatsu

AU - Wu, Xin

AU - Ogawa, Hisataka

AU - Uemura, Mamoru

AU - Nishimura, Junichi

AU - Hata, Taishi

AU - Takemasa, Ichiro

AU - Mizushima, Tsunekazu

AU - Konno, Masamitsu

AU - Doki, Yuichiro

AU - Mori, Masaki

AU - Ishii, Hideshi

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background: We previously generated induced pluripotent stem cells by reprograming adipose stem cells through the introduction of microRNAs targeting four transcription factors (Oct3/4, Sox2, c-Myc, and Klf4). In this study, we aimed to reprogram cancer cells using microRNAs to explore their therapeutic potential. Methods: Mature microRNAs (mir-302a-d, 369-3p and 5p, and mir-200c, as needed) were introduced into colon cancer cells (DLD-1, RKO, and HCT116) using lipofection. Results: The transfected cells exhibited an embryonic stem cell-like morphology and expressed the undifferentiated marker genes Nanog, Oct3/4, SOX2, and Klf4, as well as tumor-related antigen-1-60. These cells expressed neurogenic or adipogenic markers, indicating that reprogramming of the cancer cells was partially successful. Moreover, we found that miRNA-expressing DLD-1 cells showed low proliferative activity in vitro and in vivo, accompanied by increased expression of the tumor suppressor genes p16ink4a and p21waf1. miRNA-expressing DLD-1 cells also exhibited enhanced sensitivity to 5-fluorouracil, possibly through the downregulation of multidrug-resistant protein 8. The reprogrammed cells from DLD-1, RKO, and HCT116 cells exhibited reduced c-Myc expression, in contrast to the high c-Myc expression in the induced pluripotent cancer cells that were generated using four transcription factors. Conclusions: Our cancer reprogramming method employing simple lipofection of mature microRNAs is safe and well suited for clinical application, because it avoids integration of exogenous genes into the host genome and allows escape from augmentation of c-Myc gene expression.

AB - Background: We previously generated induced pluripotent stem cells by reprograming adipose stem cells through the introduction of microRNAs targeting four transcription factors (Oct3/4, Sox2, c-Myc, and Klf4). In this study, we aimed to reprogram cancer cells using microRNAs to explore their therapeutic potential. Methods: Mature microRNAs (mir-302a-d, 369-3p and 5p, and mir-200c, as needed) were introduced into colon cancer cells (DLD-1, RKO, and HCT116) using lipofection. Results: The transfected cells exhibited an embryonic stem cell-like morphology and expressed the undifferentiated marker genes Nanog, Oct3/4, SOX2, and Klf4, as well as tumor-related antigen-1-60. These cells expressed neurogenic or adipogenic markers, indicating that reprogramming of the cancer cells was partially successful. Moreover, we found that miRNA-expressing DLD-1 cells showed low proliferative activity in vitro and in vivo, accompanied by increased expression of the tumor suppressor genes p16ink4a and p21waf1. miRNA-expressing DLD-1 cells also exhibited enhanced sensitivity to 5-fluorouracil, possibly through the downregulation of multidrug-resistant protein 8. The reprogrammed cells from DLD-1, RKO, and HCT116 cells exhibited reduced c-Myc expression, in contrast to the high c-Myc expression in the induced pluripotent cancer cells that were generated using four transcription factors. Conclusions: Our cancer reprogramming method employing simple lipofection of mature microRNAs is safe and well suited for clinical application, because it avoids integration of exogenous genes into the host genome and allows escape from augmentation of c-Myc gene expression.

UR - http://www.scopus.com/inward/record.url?scp=84952876080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952876080&partnerID=8YFLogxK

U2 - 10.1245/s10434-014-4217-1

DO - 10.1245/s10434-014-4217-1

M3 - Article

C2 - 25384704

AN - SCOPUS:84952876080

VL - 22

SP - 1394

EP - 1401

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

SN - 1068-9265

ER -