ANP32A modulates cell growth by regulating p38 and Akt activity in colorectal cancer
ANP32A modulates cell growth by regulating p38 and Akt activity in colorectal cancer
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ANP32A 通过调节结直肠癌中的 p38 和 Akt 活性来调节细胞生长
DOI：
10.3892/or.2017.5845
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发表时间：
2017-09-01
期刊：
影响因子：
4.2
通讯作者：
Chen, Xu
中科院分区：
文献类型：
--
作者：
Yan, Wei;Bai, Zhun;Chen, Xu
富含亮氨酸的酸性核磷蛋白-32A(ANP32A)具有多种生化活性，已被发现在恶性肿瘤中表达减少或缺失。然而，新的发现表明，它在晚期癌症中的表达比在早期肿瘤中的表达更多。ANP32A在结直肠癌中的作用和临床意义尚不清楚。本研究采用免疫组织化学方法检测68例大肠癌组织中ANP32A的表达，并用Allred、Klein和免疫反应评分系统分析ANP32A表达与临床病理因素的关系。采用Western印迹和实时荧光定量聚合酶链式反应检测ANP32A在癌组织和正常组织中的表达及Akt和p38的活性。这些数据表明，除了大肠癌的分化程度外，ANP32A的表达与Akt和p38的活性也有显著的相关性。免疫组化和免疫印迹结果显示ANP32A在结直肠癌中高表达，在低分化肿瘤中高表达。蛋白质和信使核糖核酸分析显示，随着ANP32A的高表达，Akt在结直肠癌组织中的活性增强，而p-38的磷酸化水平降低。四甲基偶氮唑盐比色法和功能研究表明，ANP32A基因的敲除抑制了细胞的生长，诱导了p38的磷酸化和Akt的去磷酸化。本研究表明，ANP32A通过抑制p38和激活Akt信号通路促进结直肠癌的增殖，提示ANP32A可能在结直肠癌的诊断和治疗中发挥潜在作用。
Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) possesses multiple biochemical activities, has been found to be decreased or absent in malignant tumors. However, new findings have shown that it is expressed in greater amounts in advanced cancers than in early-stage tumors. The role and clinical significance of ANP32A in colorectal cancer (CRC) is still unknown. In the present study, the expression of ANP32A was assessed in 68 CRC patients by IHC, and then the correlation of its expression with clinicopathological factors was investigated using the Allred, Klein and immune response scoring system analysis. Western blot and real-time PCR analyses were used to assess ANP32A expression and the activity of Akt and p38 in cancer and normal tissues. These data indicated a significant association between ANP32A expression and the activity of Akt and p38, besides the tumor differentiation status in CRC patients. IHC and western blotting data revealed that ANP32A was overexpressed in CRC patients, and ANP32A levels were higher in poorly differentiated tumors. Protein and mRNA analysis revealed that with a high expression of ANP32A, the activation of Akt was enhanced, while the p-38 phosphorylation level was decreased in CRC tissues. MTT assay and functional studies revealed that knockdown of ANP32A inhibited cell growth and induced p38 phosphorylation and Akt dephosphorylation. The present study indicated that ANP32A promoted CRC proliferation by inhibition of p38 and activation of Akt signaling pathways and suggested that ANP32A may play a potential role in CRC diagnosis and therapy.