Silencing USP22 by asymmetric structure of interfering RNA inhibits proliferation and induces cell cycle arrest in bladder cancer cells
Silencing USP22 by asymmetric structure of interfering RNA inhibits proliferation and induces cell cycle arrest in bladder cancer cells
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通过干扰RNA的不对称结构沉默USP22可抑制膀胱癌细胞的增殖并诱导细胞周期停滞
DOI：
10.1007/s11010-010-0585-4
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发表时间：
2011-01-01
影响因子：
4.3
通讯作者：
Jiang, Guo-song
中科院分区：
文献类型：
--
作者：
Lv, Lei;Xiao, Xing-yuan;Jiang, Guo-song
泛素特异性肽酶22（USP 22）是肿瘤生长的正调节因子。然而，关于USP 22敲低对人膀胱细胞生长的影响知之甚少。在本研究中，我们设计了一系列不对称干扰RNA（aiRNA），并比较了aiRNA和传统的对称干扰RNA（siRNA）在体外和体内对人膀胱EJ细胞USP 22表达和生长的沉默效果。与USP 22特异性siRNA转染相比，15/21 aiRNA转染在下调USP 22表达和抑制体外EJ细胞增殖方面更有效。此外，用15/21 aiRNA转染的EJ细胞诱导更高频率的停滞在G 0/G1期，但不触发EJ细胞凋亡。siRNA和15/21 aiRNA均能上调EJ细胞中p53和p21的表达，下调cyclin E和Mdm 2的表达。由特异性siRNA或aiRNA诱导的上调的p53表达通过诱导Mdm 2过表达而消除。此外，用特异性siRNA或aiRNA治疗抑制小鼠中植入的人膀胱肿瘤的生长，并且aiRNA在体内具有更有效的抗肿瘤活性。因此，我们的数据表明，通过aiRNA敲低USP 22表达可能下调Mdm 2和细胞周期蛋白E的表达，导致p53和p21的表达上调，并导致细胞周期停滞和抑制人膀胱EJ细胞增殖。我们的研究结果表明，USP 22特异性aiRNA可能是干预人类膀胱肿瘤的新方法。
The ubiquitin specific peptidase 22 (USP22) is a positive regulator of the growth of tumors. However, little is known about the impact of USP22 knockdown on the growth of human bladder cells. In the present study, we designed a series of asymmetric interfering RNAs (aiRNAs) and compared the efficacy of aiRNA and conventional symmetric interfering RNA (siRNA) in the silencing of USP22 expression and the growth of human bladder EJ cells in vitro and in vivo. In comparison with transfection with the USP22-specific siRNA, transfection with 15/21 aiRNA was more potent in down-regulating the USP22 expression and inhibiting EJ cell proliferation in vitro. Furthermore, transfection with 15/21 aiRNA induced higher frequency of EJ cells arrested at the G0/G1 phases, but did not trigger EJ cell apoptosis. Moreover, transfection with either the siRNA or 15/21 aiRNA up-regulated the expression of p53 and p21, but down-regulated the expression of cyclin E and Mdm2 in EJ cells. The up-regulated p53 expression induced by the specific siRNA or aiRNA was abrogated by induction of Mdm2 over-expression. In addition, treatment with the specific siRNA or aiRNA inhibited the growth of implanted human bladder tumors in mice and the aiRNA had more potent anti-tumor activity in vivo. Therefore, our data suggest that knockdown of USP22 expression by the aiRNA may down-regulate the expression of Mdm2 and cyclin E, resulting in the up-regulated expression of p53 and p21 and leading to cell cycling arrest and inhibition of human bladder EJ cell proliferation. Our findings indicate that the USP22-specific aiRNA may be a novel approach for the intervention of human bladder tumors.