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

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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.

Original languageEnglish
Pages (from-to)915-922
Number of pages8
JournalAnnals of Surgical Oncology
Volume22
DOIs
Publication statusPublished - Dec 1 2015

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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    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, 22, 915-922. https://doi.org/10.1245/s10434-015-4554-8