Gao Su-Jun, Chen Lei, Lu Wei, Zhang Li, Wang Lu, Zhu Hai-Hang
Digestive Department of Subei People's Hospital, Clinical College of Yangzhou University, Yangzhou 225001, P.R. China.
Oncol Lett. 2018 Jun;15(6):9101-9109. doi: 10.3892/ol.2018.8461. Epub 2018 Apr 11.
MicroRNAs (miRNAs) are important regulators of tumor formation, progression and metastasis. The present study characterized a novel miRNA (miR)-888, as a potent oncomiR in human colorectal cancer (CRC). The clinicopathological investigation on 126 cases of CRC patients demonstrated that the expression level of miR-888 was significantly upregulated in tumors compared with adjacent healthy tissue, and was associated with tumor stage and histological differentiation. A Kaplan-Meier analysis and log-rank test demonstrated that CRC patients with increased miR-888 expression exhibited a decreased overall survival (OS) and disease-free survival (DFS) compared with patients with low miR-888 expression. Further univariate and multivariate analyses identified miR-888 as an independent prognostic factor for poor survival outcome in CRC patients. To determine the biological role of miR-888 in human CRC, Cell Counting kit-8, wound healing and transwell assays were performed and demonstrated that miR-888 contributed greatly to CRC cell proliferation, invasion and metastasis. Furthermore, potential targets of miR-888 were investigated using a luciferase reporter assay, followed by polymerase chain reaction and western blot analysis. The findings revealed that miR-888 directly bound to the 3'-untranslated region of mothers against decapentaplegic-4 and thus inhibited its expression and promoted the tumor growth factor-1-induced cancer metastasis signaling. The results of the present study identified miR-888 as an oncogenic miRNA in CRC and provide a foundation for promising research in the future regarding this predictive and prognostic biomarker.
微小RNA(miRNA)是肿瘤形成、进展和转移的重要调节因子。本研究鉴定了一种新型miRNA(miR)-888,它是人类结直肠癌(CRC)中一种有效的致癌miRNA。对126例CRC患者的临床病理研究表明,与相邻健康组织相比,肿瘤中miR-888的表达水平显著上调,且与肿瘤分期和组织学分化相关。Kaplan-Meier分析和对数秩检验表明,与低miR-888表达的患者相比,miR-888表达增加的CRC患者总生存期(OS)和无病生存期(DFS)降低。进一步的单因素和多因素分析确定miR-888是CRC患者生存结果差的独立预后因素。为了确定miR-888在人类CRC中的生物学作用,进行了细胞计数试剂盒-8、伤口愈合和Transwell实验,结果表明miR-888对CRC细胞增殖、侵袭和转移有很大贡献。此外,使用荧光素酶报告基因检测,随后进行聚合酶链反应和蛋白质印迹分析,研究了miR-888的潜在靶标。研究结果显示,miR-888直接与母亲对脱磷酸化蛋白-4的3'-非翻译区结合,从而抑制其表达并促进肿瘤生长因子-1诱导的癌症转移信号传导。本研究结果确定miR-888是CRC中的一种致癌miRNA,并为未来关于这种预测性和预后生物标志物的有前景的研究奠定了基础。