Wang Xu, Kuang Yuting, Shen Xiaochun, Zhou Hao, Chen Yan, Han Ye, Yuan Bin, Zhou Jin, Zhao Hong, Zhi Qiaoming, Xue Xiaofeng
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Tumour Biol. 2015 Feb;36(2):719-27. doi: 10.1007/s13277-014-2697-z. Epub 2014 Oct 7.
Aberrant expression of miR-720 had been reported in several cancers. However, the expression level and prognostic value of miR-720 in colorectal cancer (CRC) had not been addressed. In our study, we detected the expression level of miR-720 in 96 CRC tissues to evaluate its clinicopathological characteristics in colorectal cancer. Kaplan-Meier survival curve was performed to evaluate the prognostic role of miR-720 in patients with CRC. Furthermore, in vitro, we transfected the miR-720 mimics or inhibitors into the corresponding CRC cell lines and evaluated the effects on the abilities of cell growth, colony formation, migration, wound healing, and invasion in CRC cells. Our data showed that miR-720 level was significantly upregulated in CRC tissues than that in corresponding normal-appearing tissues (NATs) (p < 0.05), and high miR-720 correlated with the tumor size (p = 0.014), tumor-node-metastasis (TNM) stage (p = 0.040), lymphatic metastasis (p = 0.008), and distant metastasis (p = 0.016), which led to a poorer 5-year overall survival rate in CRC patients (p < 0.05). Our experiments in vitro also confirmed that miR-720 could promote the cell growth (p < 0.05), abilities of colony formation (p < 0.05), wound healing (p < 0.05), migration (p < 0.05), and invasion of CRC cells (p < 0.05). We identified StarD13 gene as a putative target of miR-720 in colorectal cancer by bioinformatics analysis, and subsequent dual luciferase activity and Western blot assay further certified that miR-720 might specifically target the StarD13 3'-untranslated region (UTR) at the 795 region (p < 0.05). miR-720 might act as a promoting factor in the development of CRC and could be a prognostic indicator in the prognosis of CRC. Downregulation of miR-720 might be considered to be a potentially important molecular treatment strategy for early stage CRC patients.
已有报道称miR - 720在多种癌症中存在异常表达。然而，miR - 720在结直肠癌（CRC）中的表达水平及预后价值尚未得到研究。在我们的研究中，我们检测了96例CRC组织中miR - 720的表达水平，以评估其在结直肠癌中的临床病理特征。采用Kaplan - Meier生存曲线评估miR - 720在CRC患者中的预后作用。此外，在体外实验中，我们将miR - 720模拟物或抑制剂转染至相应的CRC细胞系中，并评估其对CRC细胞生长、集落形成、迁移、伤口愈合及侵袭能力的影响。我们的数据显示，CRC组织中miR - 720水平显著高于相应的正常外观组织（NATs）（p < 0.05），且高miR - 720水平与肿瘤大小（p = 0.014）、肿瘤-淋巴结-转移（TNM）分期（p = 0.040）、淋巴转移（p = 0.008）及远处转移（p = 0.016）相关，这导致CRC患者的5年总生存率较低（p < 0.05）。我们的体外实验还证实，miR - 720可促进CRC细胞的生长（p < 0.05）、集落形成能力（p < 0.05）、伤口愈合能力（p < 0.05）、迁移能力（p < 0.05）及侵袭能力（p < 0.05）。通过生物信息学分析，我们确定StarD13基因是结直肠癌中miR - 720的一个假定靶点，随后的双荧光素酶活性和蛋白质印迹分析进一步证实，miR - 720可能特异性靶向StarD13基因3'非翻译区（UTR）的795区域（p < 0.05）。miR - 720可能在CRC的发生发展中起促进作用，并且可能是CRC预后的一个预后指标。下调miR - 720可能被认为是早期CRC患者潜在的重要分子治疗策略。
