PIK3CA expression in diffuse large B cell lymphoma tissue and the effect of its knockdown in vitro.
PIK3CA expression in diffuse large B cell lymphoma tissue and the effect of its knockdown in vitro.
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PIK3CACA在弥漫性大B细胞淋巴瘤组织中的表达及体外敲低效果
DOI：
10.2147/ott.s129970
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发表时间：
2017
影响因子：
4
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Cui W;Zheng S;Liu Z;Wang W;Cai Y;Bi R;Cao B;Zhou X
PIK 3CA已从其分子机制的角度和与其在不同类型癌症中的突变的流行病学关联进行了广泛的研究。然而，关于弥漫性大B细胞淋巴瘤（DLBCL）中PIK 3CA表达的临床病理学意义的报道很少。在本研究中，我们研究了PIK 3CA在DLBCL的临床病理意义进行免疫组织化学评价PIK 3CA在组织芯片组成的199例DLBCL。Kaplan-Meier生存分析分析PIK 3CA表达与总预后的关系。为了进一步研究PIK 3CA介导的在DLBCL细胞的增殖、细胞周期和凋亡中的作用，在使用慢病毒短发夹RNA干扰成功、稳定敲低PIK 3CA后，在DLBCL细胞系中进行细胞计数试剂盒-8（CCK-8）和流式细胞术测定。我们的研究结果表明，尽管PIK 3CA在DLBCL中广泛表达，但除体能状态（PS）和磷酸化AKT（p-AKT）表达之间外，PIK 3CA表达与临床结局或PIK 3CA表达与其他临床病理参数之间均无显著相关性。体外研究表明，在DLBCL细胞系OCI-LY 8和OCI-LY 1中，敲低PIK 3CA可显著降低细胞增殖并以G1期阻滞的方式促进细胞凋亡。此外，p27被证明是显着上调，而p-AKT和细胞周期蛋白D1被发现明显下调后，稳定敲除PIK 3CA。总之，我们的结果支持PIK 3CA在DLBCL中的致癌特性。
PIK3CA has been extensively investigated from its molecular mechanism perspective and epidemiological association with its mutations in different types of cancers. However, little has been reported regarding the clinicopathological significance of PIK3CA expression in diffuse large B cell lymphoma (DLBCL). In the present study, we investigated the clinicopathological significance of PIK3CA in DLBCL by performing immunohistochemical evaluation of PIK3CA in tissue microarrays consisting of 199 cases of DLBCL. Kaplan–Meier survival analysis was performed to analyze the association between PIK3CA expression and overall prognosis. To further investigate the role of PIK3CA mediated in the proliferation, cell cycle and apoptosis of DLBCL cells, Cell Counting Kit-8 (CCK-8) and flow cytometry assays were carried out in DLBCL cell lines after successful, stable knockdown of PIK3CA using lentiviral short hairpin RNA inference. Our results indicated that although PIK3CA was shown to be extensively expressed in DLBCL, no significant association was observed between PIK3CA expression and clinical outcome or between PIK3CA expression and other clinicopathological parameters, except between performance state (PS) and phosphorylated AKT (p-AKT) expression. In vitro studies revealed that in DLBCL cell lines OCI-LY8 and OCI-LY1, knockdown of PIK3CA could significantly reduce proliferation and promote apoptosis in a G1-phase arrested manner. Additionally, p27 was shown to be markedly upregulated, whereas p-AKT and cyclin D1 were found to be pronouncedly downregulated after stable knockdown of PIK3CA. Together, our results support the oncogenic property of PIK3CA in DLBCL.