Overexpression of Transcription Termination Factor 1 is Associated with a Poor Prognosis in Patients with Colorectal Cancer

Masami Ueda, Tomohiro Iguchi, Sho Nambara, Tomoko Saito, Hisateru Komatsu, Shotaro Sakimura, Hidenari Hirata, Ryutaro Uchi, Yuki Takano, Yoshiaki Shinden, Hidetoshi Eguchi, Takaaki Masuda, Keishi Sugimachi, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori, Koshi Mimori

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Background: RNA polymerase 1 transcription termination factor (TTF1) mediates the transcription of ribosomal RNA (rRNA). In the current study, we investigated the clinical and biological significance of the TTF1 gene in colorectal cancer (CRC). Methods: The expression of TTF1 messenger RNA (mRNA) in tumor and normal tissues from 136 patients with CRC was examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). We also performed in vitro cell proliferation and migration assays in TTF1-expressing CRC cells. The biological role of TTF1 in CRC was further elucidated using gene set enrichment analysis (GSEA) with CRC samples. Results: TTF1 expression was significantly higher in tumor tissues than in corresponding normal tissues (p = 0.016). In clinicopathological analysis, the high-TTF1 expression group showed a higher incidence of liver metastasis and lymphatic invasion than the low-TTF1 expression group (p < 0.05), and tended to have more frequent venous invasion than the low-TTF1 expression group. Furthermore, the high-TTF1 expression group had a significantly poorer prognosis than the low-TTF1 expression group (p = 0.011). Moreover, overexpression of TTF1 enhanced the proliferation and migration capacity of CRC cells in vitro. GSEA revealed that TTF1 was significantly associated with the RAS and MYC pathways, and this observation was confirmed in samples from 136 patients with CRC. Conclusion: TTF1 was involved in cancer progression via the RAS and MYC pathways in CRC, suggesting that TTF1 may be a prognostic indicator and therapeutic target in CRC.

Original languageEnglish
Pages (from-to)1490-1498
Number of pages9
JournalAnnals of Surgical Oncology
Volume22
DOIs
Publication statusPublished - Dec 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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