BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer.
BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer.
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DOI：
10.2147/ott.s118184
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发表时间：
2016
影响因子：
4
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Zhao H;Wang W;Zhao Q;Hu G;Deng K;Liu Y
癌基因和/或抑癌基因的异常表达在宫颈癌的发病机制和致瘤性中起着基础性作用。B细胞CLL/淋巴瘤3(BCL3)是一种可能存在于人类肿瘤中的原癌基因，也是CC细胞中的关键癌基因--信号转导和转录激活因子3(STAT3)。然而，其在CC中的表达状态、临床意义和生物学功能仍很不清楚。采用免疫组织化学方法检测bcl3和STAT3在癌组织中的表达。采用四甲基偶氮唑盐比色法、集落形成实验和流式细胞仪检测细胞增殖和细胞周期。与癌旁组织相比，癌组织中bcl3的表达水平明显升高。此外，免疫印迹证实，与正常宫颈上皮细胞相比，CC细胞中有高水平的bcl3蛋白表达。Bcl3阳性表达与预后不良和生存率降低相关。此外，BCL3还调节了CC细胞中STAT3的丰度。癌组织中STAT3表达上调，且与bcl3表达呈正相关。Bcl3过表达可显著促进Hela细胞的增殖和细胞周期进程。相比之下，抑制CaSki细胞中bcl3的表达显著抑制了细胞的增殖能力和细胞周期进程。体内研究表明，BCL3基因的敲除可抑制小鼠CC移植瘤的生长。值得注意的是，我们证实了STAT3介导了bcl3在CC中的致癌作用。综上所述，我们认为bcl3通过调控细胞增殖和细胞周期进程在CC中发挥癌基因的作用，其致癌作用是由其下游靶基因STAT3介导的。
Aberrant expression of oncogenes and/or tumor suppressors play a fundamental effect on the pathogenesis and tumorigenicity of cervical cancer (CC). B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and regulated signal transducer and activator of transcription 3 (STAT3), a critical oncogene, in CC cell line. However, its expression status, clinical significance and biological functions in CC remain largely unclear. The expressions of BCL3 and STAT3 in CC specimens were determined by immunohistochemistry. MTT, colony formation assays and flow cytometry analysis were carried out to test proliferation and cell cycle of CC cells. Here, the levels of BCL3 were overexpressed in CC compared to adjacent cervical tissues. Furthermore, high levels of BCL3 protein were confirmed by immunoblotting in CC cells as compared with normal cervical epithelial cells. The positive expression of BCL3 was correlated with adverse prognostic features and reduced survival rate. In addition, BCL3 regulated STAT3 abundance in CC cells. STAT3 was found to be upregulated and positively correlated with BCL3 expression in CC specimens. BCL3 overexpression resulted in prominent increased proliferation and cell cycle progression in Hela cells. By contrast, inhibition of BCL3 in CaSki cells remarkably suppressed proliferative ability and cell cycle progression. In vivo studies showed that knockdown of BCL3 inhibited tumor growth of CC in mice xenograft model. Notably, we confirmed that STAT3 mediated the oncogenic roles of BCL3 in CC. In conclusion, we suggest that BCL3 serves as an oncogene in CC by modulating proliferation and cell cycle progression, and its oncogenic effect is mediated by its downstream target gene, STAT3.