Wang Chenghai, Wang Zheng, Zhou Jie, Liu Shuang, Wu Cong, Huang Caihong, Ding Yongling
Department of Pathology, The Second Clinical Medical College, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou, China.
Department of Pathology, The First People's Hospital of Yangzhou, 368 Hanjiang Middle Road, Yangzhou, China.
Int J Cancer. 2017 Mar 15;140(6):1457-1464. doi: 10.1002/ijc.30542. Epub 2016 Dec 27.
Ultraconserved regions (UCRs) are non-protein coding gene sequences that are strictly conserved across among different species. Emerging evidence demonstrates that transcribed ultraconserved regions (TUCRs) encoding noncoding RNAs serve as regulators of gene expression. In recent decades, increasing evidence implicates the involvement of UCRs in carcinogenesis. The role of TUC.338 in cervical cancers was an oncogene in previous studies. Until now, the role of TUC.338 in colorectal cancers remains undefined. This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis. Transfection with small interfering RNA (siRNA) markedly inhibited cell migration and invasion in SW480 and HCT116 colorectal cancer cell lines. TIMP-1 was demonstrated to be negatively regulated by TUC.338 at the posttranscriptional level, via a specific target site within the 3' untranslated region by dual-luciferase reporter assay. The expression of TIMP-1 was also observed to inversely correlate with TUC.338 expression in CRC tissues. Over-expression of TIMP-1 with migRI-TIMP-1-GFP inhibited CRC cell migration and invasion and down-regulates MMP9, resembling that of TUC.338-siRNA. Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion.
超保守区域（UCRs）是在不同物种间严格保守的非蛋白质编码基因序列。新出现的证据表明，编码非编码RNA的转录超保守区域（TUCRs）可作为基因表达的调节因子。近几十年来，越来越多的证据表明UCRs参与了肿瘤发生。在先前的研究中，TUC.338在宫颈癌中扮演癌基因的角色。直到现在，TUC.338在结直肠癌中的作用仍不明确。本研究发现，TUC.338在结直肠癌（CRC）组织和CRC细胞系中显著上调，且上调的TUC.338与淋巴结转移相关。用小干扰RNA（siRNA）转染可显著抑制SW480和HCT116结直肠癌细胞系中的细胞迁移和侵袭。通过双荧光素酶报告基因检测，发现TIMP-1在转录后水平受TUC.338负调控，作用于3'非翻译区内的一个特定靶位点。在CRC组织中也观察到TIMP-1的表达与TUC.338的表达呈负相关。用migRI-TIMP-1-GFP过表达TIMP-1可抑制CRC细胞迁移和侵袭，并下调MMP9，类似于TUC.338-siRNA的作用。因此，这些发现表明，TUC.338通过靶向TIMP-1基因发挥新型癌基因的作用，从而促进结直肠癌细胞的迁移和侵袭。
