Synaptonemal complex protein 3 is a prognostic marker in cervical cancer

Hanbyoul Cho, Kyung Hee Noh, Joon Yong Chung, Mikiko Takikita, Eun Joo Chung, Bo Wook Kim, Stephen M. Hewitt, Tae Woo Kim, Jae Hoon Kim

Research output: Contribution to journalArticle

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Abstract

Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.

Original languageEnglish
Article numbere98712
JournalPloS one
Volume9
Issue number6
DOIs
Publication statusPublished - 2014 Jun 6

Fingerprint

Synaptonemal Complex
synaptonemal complex
uterine cervical neoplasms
Uterine Cervical Neoplasms
Proteins
proteins
neoplasms
Neoplasms
Tumors
Cells
cell lines
Cell Line
Cervical Intraepithelial Neoplasia
Survival

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cho, H., Noh, K. H., Chung, J. Y., Takikita, M., Chung, E. J., Kim, B. W., ... Kim, J. H. (2014). Synaptonemal complex protein 3 is a prognostic marker in cervical cancer. PloS one, 9(6), [e98712]. https://doi.org/10.1371/journal.pone.0098712
Cho, Hanbyoul ; Noh, Kyung Hee ; Chung, Joon Yong ; Takikita, Mikiko ; Chung, Eun Joo ; Kim, Bo Wook ; Hewitt, Stephen M. ; Kim, Tae Woo ; Kim, Jae Hoon. / Synaptonemal complex protein 3 is a prognostic marker in cervical cancer. In: PloS one. 2014 ; Vol. 9, No. 6.
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Cho, H, Noh, KH, Chung, JY, Takikita, M, Chung, EJ, Kim, BW, Hewitt, SM, Kim, TW & Kim, JH 2014, 'Synaptonemal complex protein 3 is a prognostic marker in cervical cancer', PloS one, vol. 9, no. 6, e98712. https://doi.org/10.1371/journal.pone.0098712

Synaptonemal complex protein 3 is a prognostic marker in cervical cancer. / Cho, Hanbyoul; Noh, Kyung Hee; Chung, Joon Yong; Takikita, Mikiko; Chung, Eun Joo; Kim, Bo Wook; Hewitt, Stephen M.; Kim, Tae Woo; Kim, Jae Hoon.

In: PloS one, Vol. 9, No. 6, e98712, 06.06.2014.

Research output: Contribution to journalArticle

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T1 - Synaptonemal complex protein 3 is a prognostic marker in cervical cancer

AU - Cho, Hanbyoul

AU - Noh, Kyung Hee

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AU - Takikita, Mikiko

AU - Chung, Eun Joo

AU - Kim, Bo Wook

AU - Hewitt, Stephen M.

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AU - Kim, Jae Hoon

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N2 - Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.

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Cho H, Noh KH, Chung JY, Takikita M, Chung EJ, Kim BW et al. Synaptonemal complex protein 3 is a prognostic marker in cervical cancer. PloS one. 2014 Jun 6;9(6). e98712. https://doi.org/10.1371/journal.pone.0098712