Center for Molecular Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, PR China.
Int J Oncol. 2012 Jul;41(1):276-84. doi: 10.3892/ijo.2012.1443. Epub 2012 Apr 20.
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.
我们之前的研究表明 UCA1 是膀胱癌的一种新型生物标志物,并通过 northern blot 分析在人膀胱移行细胞癌细胞系 BLZ-211 中检测到 UCA1 的三种变异转录本。其中一种(1.4 kb)转录本已被证明在膀胱癌的进展和胚胎发育中起着关键作用。在这项研究中,我们克隆了第二种转录本(2.2 kb),命名为 UCA1a,它与先前报道的癌症上调耐药基因(CUDR)相同。UCA1(1.4 kb 转录本)和 UCA1a(CUDR)cDNA 的序列比较显示有一个 1265 bp 的共同区域。先前的研究表明,CUDR 在多种人类肿瘤中上调,包括结肠癌、宫颈癌和肺癌。然而,UCA1a(CUDR)在膀胱癌中的确切作用尚未报道。在这项研究中,RT-PCR 分析表明 UCA1a(CUDR)也是胚胎发育和膀胱癌相关的 RNA。UCA1a(CUDR)的过表达显著增强了膀胱癌细胞系 UM-UC-2 的增殖、迁移和侵袭。此外,微阵列分析表明,UCA1a(CUDR)的过表达与调节细胞凋亡和肿瘤发生的信号通路有关。此外,UCA1a(CUDR)的过表达可以拮抗顺铂诱导的细胞凋亡,并促进 UM-UC-2 细胞在体内的致瘤性。综上所述,我们的数据强烈表明,与 UCA1 的 1.4 kb 转录本类似,UCA1a(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,它们的共同区域可能对其生物学活性至关重要,因此表明它们的共同区域可能成为膀胱癌的新治疗靶点。