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

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

The authors would like to thank Dr. Kohei Miyazono, Department of Molecular Pathology, Graduate School of Medicine, the University of Tokyo, for his technical advice; and Ms. Kazumi Oda, Michiko Kasagi, and Satoko Kono, Kyshu University Beppu Hospital, for their technical support.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan

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

  2. Department of Gastroenterology, Oita University Hospital, Yufu, Japan

    Tomoko Saito MD & Kazunari Murakami MD, PhD

  3. Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Shogo Ehata MD, PhD

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  1. Tomoko Saito MD
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  2. Junji Kurashige MD, PhD
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Corresponding author

Correspondence to Koshi Mimori MD, PhD.

Electronic supplementary material

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10434_2015_4554_MOESM1_ESM.tif

Supplementary material 1 The subgroup analysis of the prognostic significance of the lncRNA-ATB among clinical stages. 22 cases with higher expression of lncRNA-ATB was significantly worse prognosis than 18 cases of lower expression of lncRNA-ATB (p=0.018).(TIFF 80 kb)

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Saito, T., Kurashige, J., Nambara, S. et al. A Long Non-coding RNA Activated by Transforming Growth Factor-β is an Independent Prognostic Marker of Gastric Cancer. Ann Surg Oncol 22 (Suppl 3), 915–922 (2015). https://doi.org/10.1245/s10434-015-4554-8

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  • DOI: https://doi.org/10.1245/s10434-015-4554-8

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