Long non-coding RNA UCA1a(CUDR) promotes proliferation and tumorigenesis of bladder cancer
Long non-coding RNA UCA1a(CUDR) promotes proliferation and tumorigenesis of bladder cancer
复制标题
DOI：
10.3892/ijo.2012.1443
复制
发表时间：
2012-07-01
影响因子：
5.2
通讯作者：
Li, Xu
中科院分区：
文献类型：
--
作者：
Wang, Yu;Chen, Wei;Li, Xu
我们以前的研究确定UCA 1作为膀胱癌的一种新的生物标志物，并在人膀胱TCC细胞系BLZ-211中使用北方印迹分析检测到UCA 1的三种变体转录本。三种转录本中的一种（1.4 kb）已被证明在膀胱癌进展和胚胎发育中起关键作用。在这项研究中，我们克隆了第二个转录本（2.2 kb），命名为UCA 1a，这是相同的先前报告的癌症上调耐药基因（CUDR）。UCA 1（1.4 kb转录本）和UCA 1a（CUDR）cDNA的序列比较显示了1，265 bp的共同区域。先前的研究已经证明，CUDR在各种人类肿瘤中上调，包括结肠癌、宫颈癌和肺癌。然而，UCA 1a（CUDR）在膀胱癌中的确切作用尚未报道。本研究中，RT-PCR分析表明UCA 1a（CUDR）也是胚胎发育和膀胱癌相关的RNA。UCA 1a（CUDR）的过表达显著增强膀胱癌细胞系UM-UC-2的增殖、迁移和侵袭。此外，微阵列分析表明，UCA 1a（CUDR）的过表达与调节细胞凋亡和肿瘤发生的信号通路相关。UCA 1a（CUDR）过表达可拮抗顺铂诱导的UM-UC-2细胞凋亡，促进UM-UC-2细胞的体内致瘤性。综上所述，我们的数据有力地表明，类似于UCA 1的1.4 kb转录本，UCA 1a（CUDR）也可能在人类膀胱癌的生长和肿瘤发生中发挥重要作用，并且它们的共同区域可能是生物学活性的关键，从而表明它们的共同区域可能作为膀胱癌的新的治疗靶点。
Our previous studies identified UCA1 as a novel biomarker for bladder cancer and detected three variant transcripts of UCA1 in the human bladder TCC cell line BLZ-211 using northern blot analysis. One (1.4 kb) of the three transcripts has been shown to play a pivotal role in bladder cancer progression and embryonic development. In this study, we cloned a second transcript (2.2 kb), designated UCA1a, which was identical to previously reported cancer upregulated drug resistant gene (CUDR). Sequence comparison of UCA1 (1.4 kb transcript) and UCA1a(CUDR) cDNA revealed a 1,265 bp common region. Previous studies have demonstrated that CUDR is upregulated in various human tumors, including colon, cervical and lung cancer. However, the exact role of UCA1a(CUDR) in bladder cancer has not yet been reported. In this study, RT-PCR analysis indicated that UCA1a(CUDR) was also an embryonic development and bladder cancer-associated RNA. Overexpression of UCA1a(CUDR) significantly enhanced proliferation, migration and invasion of the bladder cancer cell line UM-UC-2. Moreover, microarray analysis demonstrated that overexpression of UCA1a(CUDR) was associated with signaling pathways regulating cell apoptosis and tumorigenesis. Furthermore, overexpression of UCA1a(CUDR) could antagonize cell apoptosis induced by cisplatin and promote the tumorigenicity of UM-UC-2 cells in vivo. Taken together, our data strongly suggest that similar to the 1.4 kb transcript of UCA1, UCA1a(CUDR) may also play an important role in the growth and tumorigenesis of human bladder cancer, and their common region may be critical for biological activity, thereby indicating that their common region may serve as a new therapeutic target for bladder cancer.