TY - JOUR
T1 - Overexpression of Transcription Termination Factor 1 is Associated with a Poor Prognosis in Patients with Colorectal Cancer
AU - Ueda, Masami
AU - Iguchi, Tomohiro
AU - Nambara, Sho
AU - Saito, Tomoko
AU - Komatsu, Hisateru
AU - Sakimura, Shotaro
AU - Hirata, Hidenari
AU - Uchi, Ryutaro
AU - Takano, Yuki
AU - Shinden, Yoshiaki
AU - Eguchi, Hidetoshi
AU - Masuda, Takaaki
AU - Sugimachi, Keishi
AU - Yamamoto, Hirofumi
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Mimori, Koshi
N1 - Funding Information:
This research used the super-computing resource provided by the Human Genome Center, The Institute of Medical Science, The University of Tokyo ( http://sc.hgc.jp/shirokane.html ). We thank K. Oda, M. Kasagi, S. Kono, M. Aoyagi, and T. Kawano for their excellent technical assistance. This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency; Japan Society for the Promotion of Science Grant-in-Aid for Science Research (grant numbers 21591644, 21791295, 21791297, 215921014, and 21679006); Japan Science and Technology Agency A-step (grant no. AS242Z03987P); and the Founding Program for Next Generation World-Leading Researchers (Grant no. LS094).
Publisher Copyright:
© 2015, Society of Surgical Oncology.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
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U2 - 10.1245/s10434-015-4652-7
DO - 10.1245/s10434-015-4652-7
M3 - Article
C2 - 26036188
AN - SCOPUS:84952872134
SN - 1068-9265
VL - 22
SP - 1490
EP - 1498
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
ER -