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已发表论文
Tbx2 赋予胶质母细胞瘤不良预后，并通过线粒体动力学的变化促进替莫唑胺 (Temozolomide) 耐药性
Authors Yi F, Du J, Ni W, Liu W
Received 6 October 2016
Accepted for publication 30 November 2016
Published 20 February 2017 Volume 2017:10 Pages 1059—1069
DOI https://doi.org/10.2147/OTT.S124012
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Ashok Kumar Pandurangan
Peer reviewer comments 4
Editor who approved publication: Dr Yao Dai
Abstract: Tbx2 is a
cancer-related protein that was found to be overexpressed in several human
malignancies. The present study aims to investigate the clinical significance
and biological role of Tbx2 in human astrocytoma. We examined its protein
expression in 102 cases of astrocytoma tissues using immunohistochemical
staining. Negative Tbx2 staining was observed in normal astrocytes, and
positive nuclear staining was found in 41 out of 102 astrocytoma specimens. The
rate of Tbx2 overexpression in pylocytic astrocytoma, diffuse astrocytoma,
anaplastic astrocytoma, and glioblastoma multiform (GBM) were 0%, 26.1%, 40%,
and 52%, respectively. Tbx2 overexpression correlated with poor prognosis in
patients with astrocytoma or GBM. Tbx2 plasmid transfection was performed in
A172 cells, and Tbx2 siRNA knockdown was carried out in U251 cells. Cell
Counting Kit-8, cell cycle analysis, and matrigel invasion assay showed that
Tbx2 overexpression upregulated cell proliferation, G1-S transition, and
invasion, with corresponding change of cyclin D1, p21, and MMP 2 and 9.
Importantly, we demonstrated that Tbx2 reduced apoptosis and conferred
resistance to temozolomide in GBM cell lines. Further experiments showed that
Tbx2 could regulate mitochondrial fission/fusion balance. Western blot showed
that Tbx2 overexpression reduced caspase 3 cleavage, while it induced Bcl-2 and
p-Drp1 upregulation. In conclusion, our results indicated that Tbx2 might serve
as an indicator for poor prognosis and also be useful as an important therapeutic
in human GBM, which inhibits apoptosis through regulation of mitochondrial
function.
Keywords: Tbx2, immunohistochemistry, glioblastoma, mitochondrial function
Keywords: Tbx2, immunohistochemistry, glioblastoma, mitochondrial function
