A Long Non-coding RNA Activated by Transforming Growth Factor-β is an Independent Prognostic Marker of Gastric Cancer

Tomoko Saito, Junji Kurashige, Sho Nambara, Hisateru Komatsu, Hidenari Hirata, Masami Ueda, Shotaro Sakimura, Ryutaro Uchi, Yuki Takano, Yoshiaki Shinden, Tomohiro Iguchi, Hidetoshi Eguchi, Shogo Ehata, Kazunari Murakami, Keishi Sugimachi, Koshi Mimori

研究成果: ジャーナルへの寄稿記事

61 引用 (Scopus)

抄録

Background: A recent study reported that long non-coding RNA activated by TGF-β (lncRNA-ATB) induced epithelial–mesenchymal transition (EMT) through the transforming growth factor-β (TGF-β)/miR-200s/ZEB axis in hepatocellular carcinoma. Herein, we focused on the clinical significance of lncRNA-ATB in gastric cancer (GC) patients. Materials and Methods: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to examine expression of lncRNA-ATB, miR-200b, and miR-200c in GC tissues (n = 183). Patients were divided into high and low lncRNA-ATB expression groups using a cutoff of lncRNA-ATB/GAPDH ≥0.60 or <0.60 to determine the clinicopathological significance of lncRNA-ATB in GC. Moreover, we evaluated the expression of TGF-β, lncRNA-ATB, miR-200s, and ZEB1 in GC cell lines by qRT-PCR. GC cell lines were treated by recombinant TGF-β1 or TGF-β receptor inhibitor to examine morphologic changes and genetic alterations, such as lncRNA-ATB, miR-200s, and ZEB1 levels, with respect to the EMT phenotype. Results: The high lncRNA-ATB group experienced a lower overall survival rate compared with the low lncRNA-ATB group, and multivariate analysis indicated that lncRNA-ATB was an independent prognostic factor (hazard ratio 3.50; 95 % CI 1.73–7.44; p = 0.0004). miR-200c levels were lower and ZEB1 levels were higher in the high lncRNA-ATB group than in the low lncRNA-ATB group. Treatment with TGF-β in GC cell lines resulted in morphological EMT changes, upregulation of lncRNA-ATB and ZEB1, and downregulation of miR-200c and CDH1. SB431542 reduced lncRNA-ATB expression. Conclusion: LncRNA-ATB plays an important role in EMT to promote invasion and metastasis through the TGF-β/miR-200s/ZEB axis, resulting in a poor prognosis in GC. LncRNA-ATB is a novel biomarker of lncRNA, indicative of a poor prognosis in GC patients.

元の言語英語
ページ(範囲)915-922
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

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Long Noncoding RNA
Transforming Growth Factors
Stomach Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
Cell Line
Growth Factor Receptors

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

これを引用

A Long Non-coding RNA Activated by Transforming Growth Factor-β is an Independent Prognostic Marker of Gastric Cancer. / Saito, Tomoko; Kurashige, Junji; Nambara, Sho; Komatsu, Hisateru; Hirata, Hidenari; Ueda, Masami; Sakimura, Shotaro; Uchi, Ryutaro; Takano, Yuki; Shinden, Yoshiaki; Iguchi, Tomohiro; Eguchi, Hidetoshi; Ehata, Shogo; Murakami, Kazunari; Sugimachi, Keishi; Mimori, Koshi.

:: Annals of Surgical Oncology, 巻 22, 01.12.2015, p. 915-922.

研究成果: ジャーナルへの寄稿記事

Saito, T, Kurashige, J, Nambara, S, Komatsu, H, Hirata, H, Ueda, M, Sakimura, S, Uchi, R, Takano, Y, Shinden, Y, Iguchi, T, Eguchi, H, Ehata, S, Murakami, K, Sugimachi, K & Mimori, K 2015, 'A Long Non-coding RNA Activated by Transforming Growth Factor-β is an Independent Prognostic Marker of Gastric Cancer', Annals of Surgical Oncology, 巻. 22, pp. 915-922. https://doi.org/10.1245/s10434-015-4554-8
Saito, Tomoko ; Kurashige, Junji ; Nambara, Sho ; Komatsu, Hisateru ; Hirata, Hidenari ; Ueda, Masami ; Sakimura, Shotaro ; Uchi, Ryutaro ; Takano, Yuki ; Shinden, Yoshiaki ; Iguchi, Tomohiro ; Eguchi, Hidetoshi ; Ehata, Shogo ; Murakami, Kazunari ; Sugimachi, Keishi ; Mimori, Koshi. / A Long Non-coding RNA Activated by Transforming Growth Factor-β is an Independent Prognostic Marker of Gastric Cancer. :: Annals of Surgical Oncology. 2015 ; 巻 22. pp. 915-922.
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title = "A Long Non-coding RNA Activated by Transforming Growth Factor-β is an Independent Prognostic Marker of Gastric Cancer",
abstract = "Background: A recent study reported that long non-coding RNA activated by TGF-β (lncRNA-ATB) induced epithelial–mesenchymal transition (EMT) through the transforming growth factor-β (TGF-β)/miR-200s/ZEB axis in hepatocellular carcinoma. Herein, we focused on the clinical significance of lncRNA-ATB in gastric cancer (GC) patients. Materials and Methods: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to examine expression of lncRNA-ATB, miR-200b, and miR-200c in GC tissues (n = 183). Patients were divided into high and low lncRNA-ATB expression groups using a cutoff of lncRNA-ATB/GAPDH ≥0.60 or <0.60 to determine the clinicopathological significance of lncRNA-ATB in GC. Moreover, we evaluated the expression of TGF-β, lncRNA-ATB, miR-200s, and ZEB1 in GC cell lines by qRT-PCR. GC cell lines were treated by recombinant TGF-β1 or TGF-β receptor inhibitor to examine morphologic changes and genetic alterations, such as lncRNA-ATB, miR-200s, and ZEB1 levels, with respect to the EMT phenotype. Results: The high lncRNA-ATB group experienced a lower overall survival rate compared with the low lncRNA-ATB group, and multivariate analysis indicated that lncRNA-ATB was an independent prognostic factor (hazard ratio 3.50; 95 {\%} CI 1.73–7.44; p = 0.0004). miR-200c levels were lower and ZEB1 levels were higher in the high lncRNA-ATB group than in the low lncRNA-ATB group. Treatment with TGF-β in GC cell lines resulted in morphological EMT changes, upregulation of lncRNA-ATB and ZEB1, and downregulation of miR-200c and CDH1. SB431542 reduced lncRNA-ATB expression. Conclusion: LncRNA-ATB plays an important role in EMT to promote invasion and metastasis through the TGF-β/miR-200s/ZEB axis, resulting in a poor prognosis in GC. LncRNA-ATB is a novel biomarker of lncRNA, indicative of a poor prognosis in GC patients.",
author = "Tomoko Saito and Junji Kurashige and Sho Nambara and Hisateru Komatsu and Hidenari Hirata and Masami Ueda and Shotaro Sakimura and Ryutaro Uchi and Yuki Takano and Yoshiaki Shinden and Tomohiro Iguchi and Hidetoshi Eguchi and Shogo Ehata and Kazunari Murakami and Keishi Sugimachi and Koshi Mimori",
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T1 - A Long Non-coding RNA Activated by Transforming Growth Factor-β is an Independent Prognostic Marker of Gastric Cancer

AU - Saito, Tomoko

AU - Kurashige, Junji

AU - Nambara, Sho

AU - Komatsu, Hisateru

AU - Hirata, Hidenari

AU - Ueda, Masami

AU - Sakimura, Shotaro

AU - Uchi, Ryutaro

AU - Takano, Yuki

AU - Shinden, Yoshiaki

AU - Iguchi, Tomohiro

AU - Eguchi, Hidetoshi

AU - Ehata, Shogo

AU - Murakami, Kazunari

AU - Sugimachi, Keishi

AU - Mimori, Koshi

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background: A recent study reported that long non-coding RNA activated by TGF-β (lncRNA-ATB) induced epithelial–mesenchymal transition (EMT) through the transforming growth factor-β (TGF-β)/miR-200s/ZEB axis in hepatocellular carcinoma. Herein, we focused on the clinical significance of lncRNA-ATB in gastric cancer (GC) patients. Materials and Methods: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to examine expression of lncRNA-ATB, miR-200b, and miR-200c in GC tissues (n = 183). Patients were divided into high and low lncRNA-ATB expression groups using a cutoff of lncRNA-ATB/GAPDH ≥0.60 or <0.60 to determine the clinicopathological significance of lncRNA-ATB in GC. Moreover, we evaluated the expression of TGF-β, lncRNA-ATB, miR-200s, and ZEB1 in GC cell lines by qRT-PCR. GC cell lines were treated by recombinant TGF-β1 or TGF-β receptor inhibitor to examine morphologic changes and genetic alterations, such as lncRNA-ATB, miR-200s, and ZEB1 levels, with respect to the EMT phenotype. Results: The high lncRNA-ATB group experienced a lower overall survival rate compared with the low lncRNA-ATB group, and multivariate analysis indicated that lncRNA-ATB was an independent prognostic factor (hazard ratio 3.50; 95 % CI 1.73–7.44; p = 0.0004). miR-200c levels were lower and ZEB1 levels were higher in the high lncRNA-ATB group than in the low lncRNA-ATB group. Treatment with TGF-β in GC cell lines resulted in morphological EMT changes, upregulation of lncRNA-ATB and ZEB1, and downregulation of miR-200c and CDH1. SB431542 reduced lncRNA-ATB expression. Conclusion: LncRNA-ATB plays an important role in EMT to promote invasion and metastasis through the TGF-β/miR-200s/ZEB axis, resulting in a poor prognosis in GC. LncRNA-ATB is a novel biomarker of lncRNA, indicative of a poor prognosis in GC patients.

AB - Background: A recent study reported that long non-coding RNA activated by TGF-β (lncRNA-ATB) induced epithelial–mesenchymal transition (EMT) through the transforming growth factor-β (TGF-β)/miR-200s/ZEB axis in hepatocellular carcinoma. Herein, we focused on the clinical significance of lncRNA-ATB in gastric cancer (GC) patients. Materials and Methods: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to examine expression of lncRNA-ATB, miR-200b, and miR-200c in GC tissues (n = 183). Patients were divided into high and low lncRNA-ATB expression groups using a cutoff of lncRNA-ATB/GAPDH ≥0.60 or <0.60 to determine the clinicopathological significance of lncRNA-ATB in GC. Moreover, we evaluated the expression of TGF-β, lncRNA-ATB, miR-200s, and ZEB1 in GC cell lines by qRT-PCR. GC cell lines were treated by recombinant TGF-β1 or TGF-β receptor inhibitor to examine morphologic changes and genetic alterations, such as lncRNA-ATB, miR-200s, and ZEB1 levels, with respect to the EMT phenotype. Results: The high lncRNA-ATB group experienced a lower overall survival rate compared with the low lncRNA-ATB group, and multivariate analysis indicated that lncRNA-ATB was an independent prognostic factor (hazard ratio 3.50; 95 % CI 1.73–7.44; p = 0.0004). miR-200c levels were lower and ZEB1 levels were higher in the high lncRNA-ATB group than in the low lncRNA-ATB group. Treatment with TGF-β in GC cell lines resulted in morphological EMT changes, upregulation of lncRNA-ATB and ZEB1, and downregulation of miR-200c and CDH1. SB431542 reduced lncRNA-ATB expression. Conclusion: LncRNA-ATB plays an important role in EMT to promote invasion and metastasis through the TGF-β/miR-200s/ZEB axis, resulting in a poor prognosis in GC. LncRNA-ATB is a novel biomarker of lncRNA, indicative of a poor prognosis in GC patients.

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