Liu Yanqing, Liu Rui, Yang Fei, Cheng Rongjie, Chen Xiaorui, Cui Shufang, Gu Yuanyuan, Sun Wu, You Chaoying, Liu Zhijian, Sun Feng, Wang Yanbo, Fu Zheng, Ye Chao, Zhang Chenyu, Li Jing, Chen Xi
State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Mol Cancer. 2017 Mar 4;16(1):53. doi: 10.1186/s12943-017-0625-8.
Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. T-cell intracellular antigen 1 (TIA1) is an important tumor suppressor involved in many aspects of carcinogenesis and cancer development. How TIA1 expression is regulated during CRC development remains to be carefully elucidated.
In CRC tissue sample pairs, TIA1 protein and mRNA levels were monitored by Western blot and qRT-PCR, respectively. Combining meta-analysis and miRNA target prediction software, we could predict microRNAs that targeted TIA1. Next, three CRC cell lines (SW480, Caco2 and HT29) were used to demonstrate the direct targeting of TIA1 by miR-19a. In addition, we investigated the biological effects of TIA1 inhibition by miR-19a both in vitro by CCK-8, EdU, Transwell, Ki67 immunofluorescence and Colony formation assays and in vivo by a xenograft mice model.
In colorectal cancer (CRC), we found that TIA1 protein, but not its mRNA, was downregulated. We predicted that TIA1 was a target of miR-19a and validated that miR-19a binded directly to the 3'-UTR of TIA1 mRNA. miR-19a could promote cell proliferation and migration in CRC cells and accelerated tumor growth in xenograft mice by targeting TIA1.
This study highlights an oncomiR role for miR-19a in regulating TIA1 in CRC and suggests that miR-19a may be a novel molecular therapeutic target for CRC.
由于结直肠癌（CRC）的高发病率和死亡率，它是一个全球性的主要健康问题。T细胞胞内抗原1（TIA1）是一种重要的肿瘤抑制因子，参与致癌作用和癌症发展的多个方面。在CRC发展过程中TIA1表达是如何被调控的仍有待仔细阐明。
在CRC组织样本对中，分别通过蛋白质免疫印迹法和qRT-PCR监测TIA1蛋白和mRNA水平。结合荟萃分析和miRNA靶标预测软件，我们可以预测靶向TIA1的微小RNA。接下来，使用三种CRC细胞系（SW480、Caco2和HT29）来证明miR-19a对TIA1的直接靶向作用。此外，我们通过CCK-8、EdU、Transwell、Ki67免疫荧光和集落形成试验在体外以及通过异种移植小鼠模型在体内研究了miR-19a抑制TIA1的生物学效应。
在结直肠癌（CRC）中，我们发现TIA1蛋白而非其mRNA表达下调。我们预测TIA1是miR-19a的靶标，并验证了miR-19a直接与TIA1 mRNA的3'-UTR结合。miR-19a可通过靶向TIA1促进CRC细胞的增殖和迁移，并加速异种移植小鼠中的肿瘤生长。
本研究突出了miR-19a在CRC中调控TIA1的癌基因miRNA作用，并表明miR-19a可能是CRC的一种新型分子治疗靶点。
