NCAPD3激活AKT-FOXO信号通路抑制前列腺癌细胞的凋亡-《南京师大学报（自然科学版）》

文章信息/Info

Title:: NCAPD3 Inhibits Apoptosis of Prostate Cancer Cellsby Activating AKT-FOXO Signaling Pathway

Author(s):: He Wenzheng; Wu Qingxin; Liu Ping; School of Life Sciences,Nanjing Normal University,Institute of Biochemistry and Biological Products,Nanjing 210023,China

摘要:: NCAPD3(non-SMC condensin II complex subunit D3)是condensin II复合物的亚基,其在细胞中的主要功能是调控有丝分裂时期染色质的凝缩和稳定,在前列腺癌中NCAPD3还发挥促癌的作用. 本研究探讨NCAPD3促进前列腺癌发生发展的分子机制. 首先,利用数据库分析NCAPD3在不同癌症的表达差异,再选取前列腺正常细胞和多种前列腺癌细胞为实验材料,检测p-AKT和NCAPD3的表达. 其次,分别在LNCaP中用siRNA敲低NCAPD3和DU145中过表达NCAPD3,Western blot检测AKT(Thr308和Ser473)的磷酸化水平,FOXO1/3A以及下游凋亡相关因子的表达水平,辅以流式细胞仪检测前列腺癌细胞凋亡情况. 结果表明,NCAPD3在前列腺癌中高表达,NCAPD3通过磷酸化激活AKT,进而调控FOXO1和FOXO3A的转录活性,抑制前列腺癌细胞发生凋亡作用,有利于癌细胞的生长; 最终导致前列腺癌的恶性进展. 本研究发现NCAPD3在前列腺癌中作为促癌基因,可能成为前列腺癌的一个新的临床诊断和治疗的靶基因.

Abstract:: NCAPD3(non SMC condensin II complex subunit D3)is a subunit of condensin II complex. Its main function in cells is to regulate the condensation and stabilization of chromatin during mitosis. NCAPD3 also plays a role in promoting cancer in prostate cancer. This study was to explore the molecular mechanism of NCAPD3 in promoting the development of prostate cancer. Firstly,the expression of NCAPD3 in different cancers was analyzed by using the database,and then the expression of p-AKT and NCAPD3 in normal prostate cells and various prostate cancer cells were detected. Secondly,siRNA was used to knock down NCAPD3 in LNCaP and overexpression of NCAPD3 in DU145. Western blot was used to detect the phosphorylation level of AKT(Thr308 and Ser473),the expression level of FOXO1/3A and downstream apoptosis related factors,and flow cytometry was used to detect the apoptosis of prostate cancer cells. The results showed that NCAPD3 was highly expressed in prostate cancer. NCAPD3 activated AKT through phosphorylation,and then regulated the transcriptional activities of FOXO1 and FOXO3A,inhibited the apoptosis of prostate cancer cells,and was beneficial to the growth of prostate cancer cells,eventually lead to the malignant progression of prostate cancer. This study found that NCAPD3,as a tumor promoting gene in prostate cancer,may become a new target gene for clinical diagnosis and treatment of prostate cancer.