TPX2 is a prognostic marker and promotes cell proliferation in neuroblastoma

Abstract

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 colocalization, 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 expression 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.

miR-29a Is Downregulated in Progenies Derived from Chronically Stressed Males

“…The results from these analyses indicate an upregulation of some targets related to developmental processes in offspring derived from stressed males. Target genes were overexpressed in larvae from disturbed parents ( Figure 3 A), especially those involved in the formation of some structures—such as eye ( emilin3) and axon and dendrites ( map1b )—and different markers involved in cell proliferation and DNA replication ( e2f7 , tpx2, and atad5 ) [ 44 , 45 , 46 ]. We observed the same pattern in those transcripts linked to nervous system development and neuron projection morphogenesis ( col8a1b and map1b ) [ 47 , 48 , 49 ] in our indirectly stressed progenies ( Figure 3 A).…”

LncRNA KCNQ1OT1 enhances the radioresistance of lung squamous cell carcinoma by targeting the miR-491-5p/TPX2-RNF2 axis

“…Furthermore, through bioinformatics and experimental validation, we proved that TPX2 and RNF2 might be the potential target genes of miR-491-5p. As a microtubule-associated protein, TPX2 is essential for microtubule formation and can regulate many crucial biological processes ( 69 , 70 ). The aberrant expression of TPX2 has a vital relationship with the progression of human malignant tumors ( 71 , 72 ).…”

High TPX2 expression results in poor prognosis, and Sp1 mediates the coupling of the CX3CR1/CXCL10 chemokine pathway to the PI3K/Akt pathway through targeted inhibition of TPX2 in endometrial cancer

“…TPX2 participates not only in chromosomal missegregation and aneuploidization but also in genomic instability, resulting in cell cycle progression in cancer cells. As observed for some mitosis‐related proteins, such as Ki‐67 and PCNA, overexpression of TPX2 is associated with poor prognosis in many cancers 10–12 . The ERK/GSK3β/SNAIL pathway in prostate cancer, 13 P53 pathway in breast cancer, 14 and PI3K/AKT pathway in hepatocellular cancer 15 have been found to be involved in TPX2‐related carcinogenic processes.…”

“…As observed for some mitosis‐related proteins, such as Ki‐67 and PCNA, overexpression of TPX2 is associated with poor prognosis in many cancers. 10 , 11 , 12 The ERK/GSK3β/SNAIL pathway in prostate cancer, 13 P53 pathway in breast cancer, 14 and PI3K/AKT pathway in hepatocellular cancer 15 have been found to be involved in TPX2‐related carcinogenic processes. However, to our knowledge, the clinical significance and molecular mechanism of TPX2 in EC are incompletely elucidated.…”