The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer

H. Hayashi, T. Arao, Y. Togashi, H. Kato, Y. Fujita, M. A. De Velasco, H. Kimura, K. Matsumoto, K. Tanaka, Isamu Okamoto, A. Ito, Y. Yamada, K. Nakagawa, K. Nishio

Research output: Contribution to journalArticle

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Abstract

POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4, was recently shown to be transcribed in cancer cells, but its clinical relevance and biological function have remained unclear. We now show that POU5F1B, which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B, but not OCT4, was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo, and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo. POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12%) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.

Original languageEnglish
Pages (from-to)199-208
Number of pages10
JournalOncogene
Volume34
Issue number2
DOIs
Publication statusPublished - Jan 8 2015
Externally publishedYes

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Pseudogenes
Stomach Neoplasms
Phenotype
Neoplasms
Cell Line
Growth
Human Chromosomes
Heterografts
Small Interfering RNA
Intercellular Signaling Peptides and Proteins
Transcription Factors
Up-Regulation
Messenger RNA
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Hayashi, H., Arao, T., Togashi, Y., Kato, H., Fujita, Y., De Velasco, M. A., ... Nishio, K. (2015). The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer. Oncogene, 34(2), 199-208. https://doi.org/10.1038/onc.2013.547

The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer. / Hayashi, H.; Arao, T.; Togashi, Y.; Kato, H.; Fujita, Y.; De Velasco, M. A.; Kimura, H.; Matsumoto, K.; Tanaka, K.; Okamoto, Isamu; Ito, A.; Yamada, Y.; Nakagawa, K.; Nishio, K.

In: Oncogene, Vol. 34, No. 2, 08.01.2015, p. 199-208.

Research output: Contribution to journalArticle

Hayashi, H, Arao, T, Togashi, Y, Kato, H, Fujita, Y, De Velasco, MA, Kimura, H, Matsumoto, K, Tanaka, K, Okamoto, I, Ito, A, Yamada, Y, Nakagawa, K & Nishio, K 2015, 'The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer', Oncogene, vol. 34, no. 2, pp. 199-208. https://doi.org/10.1038/onc.2013.547
Hayashi H, Arao T, Togashi Y, Kato H, Fujita Y, De Velasco MA et al. The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer. Oncogene. 2015 Jan 8;34(2):199-208. https://doi.org/10.1038/onc.2013.547
Hayashi, H. ; Arao, T. ; Togashi, Y. ; Kato, H. ; Fujita, Y. ; De Velasco, M. A. ; Kimura, H. ; Matsumoto, K. ; Tanaka, K. ; Okamoto, Isamu ; Ito, A. ; Yamada, Y. ; Nakagawa, K. ; Nishio, K. / The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer. In: Oncogene. 2015 ; Vol. 34, No. 2. pp. 199-208.
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abstract = "POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4, was recently shown to be transcribed in cancer cells, but its clinical relevance and biological function have remained unclear. We now show that POU5F1B, which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B, but not OCT4, was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo, and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo. POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12{\%}) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.",
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AU - Fujita, Y.

AU - De Velasco, M. A.

AU - Kimura, H.

AU - Matsumoto, K.

AU - Tanaka, K.

AU - Okamoto, Isamu

AU - Ito, A.

AU - Yamada, Y.

AU - Nakagawa, K.

AU - Nishio, K.

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