Induced miR-31 by 5-fluorouracil exposure contributes to the resistance in colorectal tumors

Yoshihito Nakagawa, Yuki Kuranaga, Tomomitsu Tahara, Hiromi Yamashita, Tomoyuki Shibata, Mitsuo Nagasaka, Kohei Funasaka, Naoki Omiya, Yukihiro Akao

研究成果: Article

抄録

Drug resistance makes treatment difficult in cancers. The present study identifies and analyzes drug resistance-related miRNA in colorectal cancer. We established 4 types of 5-fluorouracil (5-FU)-resistant colon cancer cell lines in vitro and in vivo. We then analyzed the miRNA expression profile by miRNA array in these 4 cell lines, and identified the drug resistance-related miRNAs. We examined the expression levels of the identified miRNA in 112 colorectal tumor samples from the patients. We identified 12 possible miRNAs involved in 5-FU resistance by miRNA arrays. We then examined the relationship between miR-31, which was the most promising among them, and drug resistance. The ectopic expression of mimic miR-31 showed significant 5-FU resistance in the parental DLD-1 cells, while anti–miR-31 caused significant growth inhibition in DLD/F cells; that is, 5-FU-resistant colon cancer cell line DLD-1 under exposure to 5-FU. When we exposed high doses of 5-FU to parent or 5-FU-resistant cells, the expression levels of miR-31 were raised higher than those of controls. Notably, the expression levels of miR-31 were positively correlated with the grade of clinical stages of colorectal tumors. The protein expression levels of factors inhibiting hypoxia-inducible factor 1 were downregulated by transfection of mimic miR-31 into DLD-1 cells. This study provides evidence supporting the association of miR-31 with 5-FU drug resistance and clinical stages of colorectal tumors.

元の言語English
ページ(範囲)2540-2548
ページ数9
ジャーナルCancer science
110
発行部数8
DOI
出版物ステータスPublished - 01-01-2019

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Fluorouracil
MicroRNAs
Colorectal Neoplasms
Drug Resistance
Cell Line
Colonic Neoplasms
Hypoxia-Inducible Factor 1
Transfection
Down-Regulation
Growth
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Nakagawa, Yoshihito ; Kuranaga, Yuki ; Tahara, Tomomitsu ; Yamashita, Hiromi ; Shibata, Tomoyuki ; Nagasaka, Mitsuo ; Funasaka, Kohei ; Omiya, Naoki ; Akao, Yukihiro. / Induced miR-31 by 5-fluorouracil exposure contributes to the resistance in colorectal tumors. :: Cancer science. 2019 ; 巻 110, 番号 8. pp. 2540-2548.
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abstract = "Drug resistance makes treatment difficult in cancers. The present study identifies and analyzes drug resistance-related miRNA in colorectal cancer. We established 4 types of 5-fluorouracil (5-FU)-resistant colon cancer cell lines in vitro and in vivo. We then analyzed the miRNA expression profile by miRNA array in these 4 cell lines, and identified the drug resistance-related miRNAs. We examined the expression levels of the identified miRNA in 112 colorectal tumor samples from the patients. We identified 12 possible miRNAs involved in 5-FU resistance by miRNA arrays. We then examined the relationship between miR-31, which was the most promising among them, and drug resistance. The ectopic expression of mimic miR-31 showed significant 5-FU resistance in the parental DLD-1 cells, while anti–miR-31 caused significant growth inhibition in DLD/F cells; that is, 5-FU-resistant colon cancer cell line DLD-1 under exposure to 5-FU. When we exposed high doses of 5-FU to parent or 5-FU-resistant cells, the expression levels of miR-31 were raised higher than those of controls. Notably, the expression levels of miR-31 were positively correlated with the grade of clinical stages of colorectal tumors. The protein expression levels of factors inhibiting hypoxia-inducible factor 1 were downregulated by transfection of mimic miR-31 into DLD-1 cells. This study provides evidence supporting the association of miR-31 with 5-FU drug resistance and clinical stages of colorectal tumors.",
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Nakagawa, Y, Kuranaga, Y, Tahara, T, Yamashita, H, Shibata, T, Nagasaka, M, Funasaka, K, Omiya, N & Akao, Y 2019, 'Induced miR-31 by 5-fluorouracil exposure contributes to the resistance in colorectal tumors', Cancer science, 巻. 110, 番号 8, pp. 2540-2548. https://doi.org/10.1111/cas.14090

Induced miR-31 by 5-fluorouracil exposure contributes to the resistance in colorectal tumors. / Nakagawa, Yoshihito; Kuranaga, Yuki; Tahara, Tomomitsu; Yamashita, Hiromi; Shibata, Tomoyuki; Nagasaka, Mitsuo; Funasaka, Kohei; Omiya, Naoki; Akao, Yukihiro.

:: Cancer science, 巻 110, 番号 8, 01.01.2019, p. 2540-2548.

研究成果: Article

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T1 - Induced miR-31 by 5-fluorouracil exposure contributes to the resistance in colorectal tumors

AU - Nakagawa, Yoshihito

AU - Kuranaga, Yuki

AU - Tahara, Tomomitsu

AU - Yamashita, Hiromi

AU - Shibata, Tomoyuki

AU - Nagasaka, Mitsuo

AU - Funasaka, Kohei

AU - Omiya, Naoki

AU - Akao, Yukihiro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Drug resistance makes treatment difficult in cancers. The present study identifies and analyzes drug resistance-related miRNA in colorectal cancer. We established 4 types of 5-fluorouracil (5-FU)-resistant colon cancer cell lines in vitro and in vivo. We then analyzed the miRNA expression profile by miRNA array in these 4 cell lines, and identified the drug resistance-related miRNAs. We examined the expression levels of the identified miRNA in 112 colorectal tumor samples from the patients. We identified 12 possible miRNAs involved in 5-FU resistance by miRNA arrays. We then examined the relationship between miR-31, which was the most promising among them, and drug resistance. The ectopic expression of mimic miR-31 showed significant 5-FU resistance in the parental DLD-1 cells, while anti–miR-31 caused significant growth inhibition in DLD/F cells; that is, 5-FU-resistant colon cancer cell line DLD-1 under exposure to 5-FU. When we exposed high doses of 5-FU to parent or 5-FU-resistant cells, the expression levels of miR-31 were raised higher than those of controls. Notably, the expression levels of miR-31 were positively correlated with the grade of clinical stages of colorectal tumors. The protein expression levels of factors inhibiting hypoxia-inducible factor 1 were downregulated by transfection of mimic miR-31 into DLD-1 cells. This study provides evidence supporting the association of miR-31 with 5-FU drug resistance and clinical stages of colorectal tumors.

AB - Drug resistance makes treatment difficult in cancers. The present study identifies and analyzes drug resistance-related miRNA in colorectal cancer. We established 4 types of 5-fluorouracil (5-FU)-resistant colon cancer cell lines in vitro and in vivo. We then analyzed the miRNA expression profile by miRNA array in these 4 cell lines, and identified the drug resistance-related miRNAs. We examined the expression levels of the identified miRNA in 112 colorectal tumor samples from the patients. We identified 12 possible miRNAs involved in 5-FU resistance by miRNA arrays. We then examined the relationship between miR-31, which was the most promising among them, and drug resistance. The ectopic expression of mimic miR-31 showed significant 5-FU resistance in the parental DLD-1 cells, while anti–miR-31 caused significant growth inhibition in DLD/F cells; that is, 5-FU-resistant colon cancer cell line DLD-1 under exposure to 5-FU. When we exposed high doses of 5-FU to parent or 5-FU-resistant cells, the expression levels of miR-31 were raised higher than those of controls. Notably, the expression levels of miR-31 were positively correlated with the grade of clinical stages of colorectal tumors. The protein expression levels of factors inhibiting hypoxia-inducible factor 1 were downregulated by transfection of mimic miR-31 into DLD-1 cells. This study provides evidence supporting the association of miR-31 with 5-FU drug resistance and clinical stages of colorectal tumors.

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