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Article

Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma

  • Authors:
    • Hisateru Komatsu
    • Tomohiro Iguchi
    • Masami Ueda
    • Sho Nambara
    • Tomoko Saito
    • Hidenari Hirata
    • Shotaro Sakimura
    • Yuki Takano
    • Ryutaro Uchi
    • Yoshiaki Shinden
    • Hidetoshi Eguchi
    • Takaaki Masuda
    • Keishi Sugimachi
    • Hidetoshi Eguchi
    • Yuichiro Doki
    • Masaki Mori
    • Koshi Mimori
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Kyushu University, Beppu Hospital, Beppu, Oita, Japan, Department of Gastroenterological Surgery, Graduate School of Medicine, Suita, Osaka, Japan
  • Pages: 2073-2080
    |
    Published online on: January 25, 2016
       https://doi.org/10.3892/or.2016.4593
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Abstract

Recent studies have indicated that increased ribosomal activity contributes to cancer progression. Transcription termination factor, RNA polymerase I (TTF1) acts as a transcription factor for RNA polymerase I. However, the role which TTF1 plays in cancer progression still remains unknown. The present study aimed to determine whether TTF1 plays a critical role in the progression of human liver hepatocellular carcinoma (HCC). In the present study, quantitative real-time reverse transcription polymerase chain reaction was conducted to evaluate TTF1 mRNA expression in 60 HCC tissue samples in order to determine the clinicopathological significance of TTF1. To investigate whether the expression levels of TTF1 were associated known gene signatures which represented ribosomal activity, we applied gene set enrichment analysis (GSEA) to HCC cases in The Cancer Genome Atlas (TCGA) a. We also performed in vitro proliferation assays using TTF1‑overexpressing HCC cells. TTF1 expression was significantly higher in HCC tumor tissues than in adjacent liver tissues (P<0.001). The overall survival (OS) of patients with high TTF1 expression levels was significantly shorter than that of patients with low TTF1 expression (P=0.027). Multivariate analysis indicated that TTF1 expression was an independent prognostic factor for OS (P=0.020). GSEA revealed significant associations between TTF1 expression and gene sets involved in ribosomal function. In vitro, cell proliferation and rRNA transcription were significantly promoted by overexpression of TTF1 in the HCC cell lines HuH-7 and HepG2. From these results, it was suggested that TTF1 participate in poor prognoses and play a role in tumor cell growth in HCC, possibly by upregulating ribosomal activity. In conclusion, we first propose that TTF1 may be a novel biomarker and therapeutic target in HCC. Increased expression of TTF1 was significantly associated with poor prognosis in two independent sets of HCC cases. Furthermore, in vitro experiments provided an explanation for clinical data showing that overexpression of TTF1 contributed to the proliferation of cancer cells.
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View References

1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Perz JF, Armstrong GL, Farrington LA, Hutin YJ and Bell BP: The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 45:529–538. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Busch H, Byvoet P and Smetana K: The nucleolus of the cancer cell: A review. Cancer Res. 23:313–339. 1963.PubMed/NCBI

4 

Nguyen XT, Chan SM, Ngo TD, Raval A, Kim KK, Majeti R and Mitchell BS: Interaction of TIF-90 and filamin A in the regulation of rRNA synthesis in leukemic cells. Blood. 124:579–589. 2014. View Article : Google Scholar

5 

Noller HF: Structure of ribosomal RNA. Annu Rev Biochem. 53:119–162. 1984. View Article : Google Scholar : PubMed/NCBI

6 

Arabi A, Wu S, Ridderstråle K, Bierhoff H, Shiue C, Fatyol K, Fahlén S, Hydbring P, Söderberg O, Grummt I, et al: c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nat Cell Biol. 7:303–310. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Grandori C, Gomez-Roman N, Felton-Edkins ZA, Ngouenet C, Galloway DA, Eisenman RN and White RJ: c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol. 7:311–318. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Grummt I and Pikaard CS: Epigenetic silencing of RNA polymerase I transcription. Nat Rev Mol Cell Biol. 4:641–649. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Lessard F, Morin F, Ivanchuk S, Langlois F, Stefanovsky V, Rutka J and Moss T: The ARF tumor suppressor controls ribosome biogenesis by regulating the RNA polymerase I transcription factor TTF-I. Mol Cell. 38:539–550. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Sander EE, Mason SW, Munz C and Grummt I: The amino-terminal domain of the transcription termination factor TTF-I causes protein oligomerization and inhibition of DNA binding. Nucleic Acids Res. 24:3677–3684. 1996. View Article : Google Scholar : PubMed/NCBI

11 

Evers R, Smid A, Rudloff U, Lottspeich F and Grummt I: Different domains of the murine RNA polymerase I-specific termination factor mTTF-I serve distinct functions in transcription termination. EMBO J. 14:1248–1256. 1995.PubMed/NCBI

12 

Kuhn A, Bartsch I and Grummt I: Specific interaction of the murine transcription termination factor TTF I with class-I RNA polymerases. Nature. 344:559–562. 1990. View Article : Google Scholar : PubMed/NCBI

13 

Längst G, Blank TA, Becker PB and Grummt I: RNA polymerase I transcription on nucleosomal templates: The transcription termination factor TTF-I induces chromatin remodeling and relieves transcriptional repression. EMBO J. 16:760–768. 1997. View Article : Google Scholar : PubMed/NCBI

14 

Lessard F, Stefanovsky V, Tremblay MG and Moss T: The cellular abundance of the essential transcription termination factor TTF-I regulates ribosome biogenesis and is determined by MDM2 ubiquitinylation. Nucleic Acids Res. 40:5357–5367. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Ruan Y, Sun L, Hao Y, Wang L, Xu J, Zhang W, Xie J, Guo L, Zhou L, Yun X, et al: Ribosomal RACK1 promotes chemoresistance and growth in human hepatocellular carcinoma. J Clin Invest. 122:2554–2566. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Roessler S, Jia HL, Budhu A, Forgues M, Ye QH, Lee JS, Thorgeirsson SS, Sun Z, Tang ZY, Qin LX, et al: A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients. Cancer Res. 70:10202–10212. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Wen F, Zhou R, Shen A, Choi A, Uribe D and Shi J: The tumor suppressive role of eIF3f and its function in translation inhibition and rRNA degradation. PLoS One. 7:e341942012. View Article : Google Scholar : PubMed/NCBI

19 

Takada H and Kurisaki A: Emerging roles of nucleolar and ribosomal proteins in cancer, development, and aging. Cell Mol Life Sci. 72:4015–4025. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Nakamura T, Rapp F and Busch H: Common features of the base composition of rapidly labeled RNA of nucleoli in a number of experimental tumors. Cancer Res. 27:1084–1091. 1967.PubMed/NCBI

21 

Albertson DG: Gene amplification in cancer. Trends Genet. 22:447–455. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Sirri V, Roussel P, Trerè D, Derenzini M and Hernandez-Verdun D: Amount variability of total and individual Ag-NOR proteins in cells stimulated to proliferate. J Histochem Cytochem. 43:887–893. 1995. View Article : Google Scholar : PubMed/NCBI

23 

Tannapfel A, Geissler F, Köckerling F, Katalinic A, Hauss J and Wittekind C: Apoptosis and proliferation in relation to histopathological variables and prognosis in hepatocellular carcinoma. J Pathol. 187:439–445. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Torres-Montaner A, Bolivar J, Ortiz M and Valdivia MM: Immunohistochemical detection of ribosomal transcription factor UBF: Diagnostic value in malignant specimens. J Pathol. 184:77–82. 1998. View Article : Google Scholar : PubMed/NCBI

25 

Ito Y, Matsuura N, Sakon M, Takeda T, Umeshita K, Nagano H, Nakamori S, Dono K, Tsujimoto M, Nakahara M, et al: Both cell proliferation and apoptosis significantly predict shortened disease-free survival in hepatocellular carcinoma. Br J Cancer. 81:747–751. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Kusnadi EP, Hannan KM, Hicks RJ, Hannan RD, Pearson RB and Kang J: Regulation of rDNA transcription in response to growth factors, nutrients and energy. Gene. 556:27–34. 2015. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Komatsu H, Iguchi T, Ueda M, Nambara S, Saito T, Hirata H, Sakimura S, Takano Y, Uchi R, Shinden Y, Shinden Y, et al: Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma. Oncol Rep 35: 2073-2080, 2016.
APA
Komatsu, H., Iguchi, T., Ueda, M., Nambara, S., Saito, T., Hirata, H. ... Mimori, K. (2016). Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma. Oncology Reports, 35, 2073-2080. https://doi.org/10.3892/or.2016.4593
MLA
Komatsu, H., Iguchi, T., Ueda, M., Nambara, S., Saito, T., Hirata, H., Sakimura, S., Takano, Y., Uchi, R., Shinden, Y., Eguchi, H., Masuda, T., Sugimachi, K., Eguchi, H., Doki, Y., Mori, M., Mimori, K."Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma". Oncology Reports 35.4 (2016): 2073-2080.
Chicago
Komatsu, H., Iguchi, T., Ueda, M., Nambara, S., Saito, T., Hirata, H., Sakimura, S., Takano, Y., Uchi, R., Shinden, Y., Eguchi, H., Masuda, T., Sugimachi, K., Eguchi, H., Doki, Y., Mori, M., Mimori, K."Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma". Oncology Reports 35, no. 4 (2016): 2073-2080. https://doi.org/10.3892/or.2016.4593
Copy and paste a formatted citation
x
Spandidos Publications style
Komatsu H, Iguchi T, Ueda M, Nambara S, Saito T, Hirata H, Sakimura S, Takano Y, Uchi R, Shinden Y, Shinden Y, et al: Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma. Oncol Rep 35: 2073-2080, 2016.
APA
Komatsu, H., Iguchi, T., Ueda, M., Nambara, S., Saito, T., Hirata, H. ... Mimori, K. (2016). Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma. Oncology Reports, 35, 2073-2080. https://doi.org/10.3892/or.2016.4593
MLA
Komatsu, H., Iguchi, T., Ueda, M., Nambara, S., Saito, T., Hirata, H., Sakimura, S., Takano, Y., Uchi, R., Shinden, Y., Eguchi, H., Masuda, T., Sugimachi, K., Eguchi, H., Doki, Y., Mori, M., Mimori, K."Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma". Oncology Reports 35.4 (2016): 2073-2080.
Chicago
Komatsu, H., Iguchi, T., Ueda, M., Nambara, S., Saito, T., Hirata, H., Sakimura, S., Takano, Y., Uchi, R., Shinden, Y., Eguchi, H., Masuda, T., Sugimachi, K., Eguchi, H., Doki, Y., Mori, M., Mimori, K."Clinical and biological significance of transcription termination factor, RNA polymerase I in human liver hepatocellular carcinoma". Oncology Reports 35, no. 4 (2016): 2073-2080. https://doi.org/10.3892/or.2016.4593
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