Disruption of serine/threonine protein phosphatase 5 inhibits tumorigenesis of urinary bladder cancer cells.
Disruption of serine/threonine protein phosphatase 5 inhibits tumorigenesis of urinary bladder cancer cells.
复制标题
丝氨酸/苏氨酸蛋白磷酸酶5的破坏抑制膀胱癌细胞的肿瘤发生
DOI：
10.3892/ijo.2017.3997
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发表时间：
2017-07
影响因子：
5.2
通讯作者：
Xu DF
中科院分区：
文献类型：
--
作者：
Chen M;Lv JM;Ye JQ;Cui XG;Qu FJ;Chen L;Liu X;Pan XW;Li L;Huang H;Yang QW;Chen J;Wang LH;Gao Y;Xu DF
丝氨酸/苏氨酸蛋白磷酸酶5 （PPP5C）是蛋白丝氨酸/苏氨酸磷酸酶家族的成员，已被证明参与多种信号级联反应和肿瘤进展。我们通过ONCOMINE微阵列数据挖掘发现，与正常尿路上皮组织相比，PPP5C在膀胱癌组织中高表达，并且与肿瘤分期呈正相关。通过慢病毒介导的短发夹RNA （shRNA）敲低PPP5C可显著抑制细胞增殖和集落形成。流式细胞术分析显示，ppp5c缺失的T24和BT5637膀胱癌细胞被阻滞在G0/G1期并诱导凋亡。此外，在异种移植裸鼠模型中，肿瘤生长受到抑制。进一步的研究表明，PPP5C的下调下调了c-myc和CDK4，而上调了p27、BAD和Beclin1。这些结果提示PPP5C与膀胱癌（BCa）相关，并在膀胱癌的发生发展中起致瘤作用。
Serine/threonine protein phosphatase 5 (PPP5C) is a member of the protein serine/threonine phosphatase family and has been shown to participate in multiple signaling cascades and tumor progression. We found that PPP5C was highly expressed in bladder cancer tissues compared to normal urothelial tissues, and positively correlated to tumor stages through ONCOMINE microarray data mining. Knockdown of PPP5C via a lentivirus-mediated short hairpin RNA (shRNA) markedly inhibited cell proliferation and colony formation. Flow cytometric analysis showed that PPP5C-deficient T24 and BT5637 bladder cancer cells were arrested in G0/G1 phase and induced apoptosis. In addition, tumor growth was inhibited in vivo in a xenograft nude mouse model. Further studies indicated that knockdown of PPP5C downregulated c-myc and CDK4, whereas upregulated p27, BAD and Beclin1. These results suggest that PPP5C is associated with bladder cancer (BCa) and plays an oncogenic role in the development and progression of bladder cancer.