TY - JOUR
T1 - TPX2 is a prognostic marker and promotes cell proliferation in neuroblastoma
AU - Koike, Yuhki
AU - Yin, Chengzeng
AU - Sato, Yuki
AU - Nagano, Yuka
AU - Yamamoto, Akira
AU - Kitajima, Takahito
AU - Shimura, Tadanobu
AU - Kawamura, Mikio
AU - Matsushita, Kohei
AU - Okugawa, Yoshinaga
AU - Amano, Keishiro
AU - Otake, Kohei
AU - Okita, Yoshiki
AU - Ohi, Masaki
AU - Inoue, Mikihiro
AU - Uchida, Keiichi
AU - Hirayama, Masahiro
AU - Toiyama, Yuji
N1 - Publisher Copyright:
© 2022 Spandidos Publications. All rights reserved.
PY - 2022/4
Y1 - 2022/4
N2 - Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is upregulated in various tumors, and several studies have demonstrated the role of TPX2 as a prognostic marker in cancer. However, the function of TPX2 in neuroblastoma (NB) has not been completely elucidated. In the present study, the clinical significance and functional role of TPX2 in NB was investigated. The Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-NB dataset was used. A total of 43 patients with NB were enrolled in the present study as the validation set. After evaluating the prognostic role of TPX2, the combined predictive effect of TPX2 and MYCN proto-oncogene bHLH transcription factor (MYCN) gene amplification was assessed. Double immunofluorescence staining for TPX2 and N-Myc was used to analyze colocaliza- tion, and multiple cell function tests were performed by means of in vitro experiments to elucidate the functional role of TPX2 using RNA interference technology in NB cell lines. In both the TARGET-NB set and the validation set, it was found that upregulated of TPX2 was significantly associated with poor overall survival (OS) in patients with NB. The expres- sion of TPX2 was higher in NB patients with MYCN gene amplification, and NB patients with high TPX2 expression and MYCN gene amplification had the poorest OS compared with patients with low TPX2 expression or a single copy of MYCN. In vitro experiments indicated that TPX2 positively regulated cell proliferation and the cell cycle, and promoted cell survival by increasing the resistance to apoptosis. The colocalization of TPX2 with N-Myc in NB cells and tissue was observed. The findings of the present study indicate that TPX2 plays an oncogenic role in NB development and may be a potential prognostic indicator in patients with NB.
AB - Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is upregulated in various tumors, and several studies have demonstrated the role of TPX2 as a prognostic marker in cancer. However, the function of TPX2 in neuroblastoma (NB) has not been completely elucidated. In the present study, the clinical significance and functional role of TPX2 in NB was investigated. The Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-NB dataset was used. A total of 43 patients with NB were enrolled in the present study as the validation set. After evaluating the prognostic role of TPX2, the combined predictive effect of TPX2 and MYCN proto-oncogene bHLH transcription factor (MYCN) gene amplification was assessed. Double immunofluorescence staining for TPX2 and N-Myc was used to analyze colocaliza- tion, and multiple cell function tests were performed by means of in vitro experiments to elucidate the functional role of TPX2 using RNA interference technology in NB cell lines. In both the TARGET-NB set and the validation set, it was found that upregulated of TPX2 was significantly associated with poor overall survival (OS) in patients with NB. The expres- sion of TPX2 was higher in NB patients with MYCN gene amplification, and NB patients with high TPX2 expression and MYCN gene amplification had the poorest OS compared with patients with low TPX2 expression or a single copy of MYCN. In vitro experiments indicated that TPX2 positively regulated cell proliferation and the cell cycle, and promoted cell survival by increasing the resistance to apoptosis. The colocalization of TPX2 with N-Myc in NB cells and tissue was observed. The findings of the present study indicate that TPX2 plays an oncogenic role in NB development and may be a potential prognostic indicator in patients with NB.
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U2 - 10.3892/ol.2022.13256
DO - 10.3892/ol.2022.13256
M3 - Article
AN - SCOPUS:85126652456
SN - 1792-1074
VL - 23
JO - Oncology Letters
JF - Oncology Letters
IS - 4
M1 - 136
ER -