PBX3 is associated with proliferation and poor prognosis in patients with cervical cancer.
PBX3 is associated with proliferation and poor prognosis in patients with cervical cancer.
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PBX3与宫颈癌患者的增殖和不良预后相关
DOI：
10.2147/ott.s150139
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发表时间：
2017
影响因子：
4
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Li H;Sun G;Liu C;Wang J;Jing R;Wang J;Zhao X;Xu X;Yang Y
前B细胞白血病同源框3（PBX 3）在各种恶性肿瘤中上调;然而，PBX 3在宫颈癌（CC）中的作用尚不清楚。本研究旨在探讨PBMC 3在CC中的表达特点、临床病理意义及分子生物学功能。通过实时荧光定量PCR（RT-PCR）、Western blotting和免疫组化染色分析PBMC 3在CC细胞系和肿瘤标本中的表达水平。评估与PBX 3表达相关的临床病理特征。采用RNA干扰方法在体外和体内抑制CC中PBX 3的表达，确定其在细胞增殖中的作用并分析其分子功能。我们发现，与正常细胞和邻近的非肿瘤性宫颈组织相比，在CC细胞系和临床标本中，PBX 3的表达显著上调。PBX 3表达与肿瘤直径、病理分级、淋巴结转移、浸润深度、血管浸润及临床分期相关，是预后不良的独立预测因子。多因素分析提示，PBX 3表达可能是CC患者生存的独立预后指标。与PBX 3低表达的患者相比，PBX 3高表达的CC患者的总生存率降低。此外，稳定下调CC细胞系中的PBX 3表达抑制细胞增殖并降低体外p-AKT蛋白表达水平。类似地，体内测定表明，CC细胞中的PBX 3下调显著抑制肿瘤大小和重量。总之，我们证明了PBX 3可以通过AKT信号通路促进CC细胞增殖，并且它可以作为预后标志物。我们的数据表明，PBX 3的失活可能是一种有效的临床治疗CC。
Pre-B-cell leukemia homeobox 3 (PBX3) is upregulated in various malignancies; however, the role of PBX3 in cervical cancer (CC) is unknown. The purpose of this study was to explore the expression characteristics, clinicopathological significance, and molecular biological function of PBX3 in CC. The expression levels of PBX3 were analyzed in CC cell lines and tumor specimens by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining. The clinicopathological characteristics associated with PBX3 expression were evaluated. An RNA interference approach was employed to suppress PBX3 expression in CC in vitro and in vivo, determine its role in cell proliferation and analyze its molecular function. We found that PBX3 expression was significantly upregulated in CC cell lines and clinical specimens compared with normal cells and adjacent nontumorous cervical tissues. PBX3 was an independent predictive factor of poor prognosis, and its expression was correlated with tumor diameter, pathological grading, lymph node metastasis, invasion depth, vascular invasion, and clinical stage of CC. Multivariate analysis suggested that PBX3 expression may represent an independent prognostic indicator of the survival of CC patients. CC patients with high PBX3 expression exhibited reduced overall survival compared with those with low PBX3 expression. Additionally, stable downregulation of PBX3 expression in CC cell lines suppressed cell proliferation and decreased p-AKT protein expression levels in vitro. Similarly, in vivo assays demonstrated that PBX3 downregulation in CC cells markedly inhibited tumor size and weight. Overall, we demonstrated that PBX3 can promote CC cell proliferation via the AKT signaling pathway and that it may serve as a prognostic marker. Our data indicate that inactivation of PBX3 may be an effective clinical treatment for CC.