Xue Yao, Ma Gaoxiang, Zhang Zhensheng, Hua Qiuhan, Chu Haiyan, Tong Na, Yuan Lin, Qin Chao, Yin Changjun, Zhang Zhengdong, Wang Meilin
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of Urology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
Oncotarget. 2015 Jan 1;6(1):484-93. doi: 10.18632/oncotarget.2861.
Antisense long noncoding RNAs (lncRNAs) play important roles in regulating the expression of coding genes in post-transcriptional level. However, detailed expression profile of lncRNAs and functions of antisense lncRNAs in bladder cancer remains unclear. To investigate regulation of lncRNAs in bladder cancer and demonstrate their functions, we performed lncRNAs microarray analysis in 3 paired bladder cancer tissues. Further molecular assays were conducted to determine the potential role of identified antisense lncRNA MDC1-AS. As a result, a series of lncRNAs were differentially expressed in bladder cancer tissues in microarray screen. In a larger size of samples validation, we found that the expression levels of MDC1-AS and MDC1 was down-regulated in bladder cancer. After over-expression of MDC1-AS, increased levels of MDC1 were observed in bladder cancer cells. We also found a remarkably inhibitory role of antisense lncRNA MDC1-AS on malignant cell behaviors in bladder cancer cells EJ and T24. Subsequently, knockdown of MDC1 revealed that suppressing role of MDC1-AS was attributed to up-regulation of MDC1. In summary, we have identified a novel antisense lncRNA MDC1-AS, which may participate in bladder cancer through up-regulation of its antisense tumor-suppressing gene MDC1. Further studies should be conducted to demonstrate detailed mechanism of our findings.
反义长链非编码RNA（lncRNAs）在转录后水平调控编码基因的表达中发挥着重要作用。然而，lncRNAs的详细表达谱以及反义lncRNAs在膀胱癌中的功能仍不清楚。为了研究lncRNAs在膀胱癌中的调控作用并阐明其功能，我们对3对膀胱癌组织进行了lncRNAs微阵列分析。进一步进行分子检测以确定已鉴定的反义lncRNA MDC1-AS的潜在作用。结果，在微阵列筛选中一系列lncRNAs在膀胱癌组织中差异表达。在更大样本量的验证中，我们发现MDC1-AS和MDC1的表达水平在膀胱癌中下调。过表达MDC1-AS后，在膀胱癌细胞中观察到MDC1水平升高。我们还发现反义lncRNA MDC1-AS对膀胱癌细胞EJ和T24中的恶性细胞行为具有显著的抑制作用。随后，敲低MDC1表明MDC1-AS的抑制作用归因于MDC1的上调。总之，我们鉴定出一种新的反义lncRNA MDC1-AS，其可能通过上调其反义抑癌基因MDC1参与膀胱癌的发生。应进一步开展研究以阐明我们研究结果的详细机制。
