PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion, metastasis and growth.
PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion, metastasis and growth.
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miR-146-3p调控的PTTG1促进膀胱癌迁移、侵袭、转移和生长
DOI：
10.18632/oncotarget.13507
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发表时间：
2017-01-03
期刊：
影响因子：
--
通讯作者：
Zeng F
中科院分区：
文献类型：
--
作者：
Xiang W;Wu X;Huang C;Wang M;Zhao X;Luo G;Li Y;Jiang G;Xiao X;Zeng F
PTTG 1是一种癌基因，在许多肿瘤中过度表达。然而，PTTG 1在膀胱癌（BC）中的作用尚未得到很好的表征。在本研究中，我们发现PTTG 1 mRNA和蛋白在BC组织和细胞中的表达均显著增加。PTTG 1蛋白表达与肿瘤大小、TNM分期、淋巴管浸润和远处转移呈正相关。PTTG 1基因敲低可显著抑制BC细胞的迁移、侵袭、转移和生长，并诱导BC细胞衰老和细胞周期阻滞于G 0/G1期。通过靶点预测算法和荧光素酶报告基因分析，进一步确定PTTG 1是miR-146 a-3 p的直接靶点。miR-146 a-3 p在BC组织和细胞中呈低表达，且与PTTG 1水平呈负相关。miR-146 a-3 p过表达可抑制BC细胞的迁移、侵袭、转移和生长，并诱导BC细胞衰老。拯救实验表明，与PTTG 1过表达相比，miR-146 a-3 p和PTTG 1的异位表达抑制了BC细胞的迁移、侵袭并诱导了细胞周期停滞和衰老，证实了miR-146 a-3 p通过靶向PTTG 1抑制BC进展。综上所述，我们的研究发现miR-146 a-3 p/PTTG 1轴调控BC的迁移、侵袭、转移和生长，可能成为BC治疗的靶点。
Pituitary tumor-transforming gene 1 (PTTG1) is identified as an oncogene, and overexpresses in many tumors. However, the role of PTTG1 in bladder cancer (BC) hasn't yet been characterized well. In this study, we showed the expression of PTTG1 mRNA and protein were both significantly increased in BC tissues and cells. The PTTG1 protein levels were positive correlated with increased tumor size, tumor–node–metastasis (TNM) stage, lymphatic invasion and distant metastasis of BC. PTTG1 knockdown dramatically suppressed the migration, invasion, metastasis and growth, and induced senescence and cell-cycle arrest at G0/G1 phase of BC cells. We further identified PTTG1 was the direct target of miR-146a-3p through using target prediction algorithms and luciferase reporter assay. miR-146a-3p was low expressed and negatively correlated with PTTG1 levels in BC tissues and cells. miR-146a-3p overexpression inhibited migration, invasion, metastasis and growth, and induced senescence of BC cells. Rescue experiment suggested ectopic expression of miR-146a-3p and PTTG1 suppressed migration, invasion and induced cell cycle arrest and senescence of BC cells compared to PTTG1 overexpression, confirming miR-146a-3p inhibited BC progression by targeting PTTG1. In summary, our study found miR-146a-3p/PTTG1 axis regulated BC migration, invasion, metastasis and growth, and might be a targets for BC therapy.
影响因子：
3.8
作者：
Hidalgo M;Galan JJ;Sáez C;Ferrero E;Castilla C;Ramirez-Lorca R;Pelaez P;Ruiz A;Japón MA;Royo JL
通讯作者：
Royo JL