Department of Medical Oncology, The First People's Hospital of Yancheng, The Fourth Affiliated Hospital, Medical School of Nantong University, No. 14 Yuehe Road, Tinghu District, Yancheng, 224001, Jiangsu, People's Republic of China,
Mol Cell Biochem. 2013 Nov;383(1-2):49-58. doi: 10.1007/s11010-013-1753-0. Epub 2013 Jul 11.
Increasing evidence suggests that dysregulation of microRNAs is correlated with malignant transformation and tumor development. miR-100, a potential tumor suppressor, is downregulated by many human cancers. However, the expression and functions of miR-100 in hepatocellular carcinoma (HCC) are still unclear. The aim of this study was to detect the expression of miR-100 in HCC tissues and investigate its clinicopathological and prognostic significance. Also, the effects of miR-100 on growth and apoptosis of HCC cells and its potential molecular mechanisms were analyzed. Results showed that the expression level of miR-100 in HCC tissues was significantly lower than that in matched non-cancerous liver tissues. Also, low-miR-100 expression was observed to be significantly correlated with higher tumor grade, higher incidence of lymph node metastasis, advanced TNM stage and higher incidence of tumor recurrence in HCC patients. Multivariate survival analyses suggested that low-miR-100 expression was an independent prognostic factor for HCC patients (HR = 1.66, 95 % CI 1.32-2.82, P = 0.019). In addition, we found that upregulation of miR-100 could inhibit growth and increase apoptosis of HCC cells by downregulating polo-like kinase 1 (plk1). In HCC tissues, miR-100 expression was inversely correlated with the expression of plk1 protein (r = -0.418; P = 0.029). Therefore, downregulation of miR-100 was correlated with progressive pathological feature and poor prognosis in HCC patients, and miR-100 could function as a tumor suppressor by targeting plk1. miR-100 may serve as a prognostic marker and molecular therapeutic target in HCC.
越来越多的证据表明,miRNA 的失调与恶性转化和肿瘤发展有关。miR-100 是一种潜在的肿瘤抑制因子,许多人类癌症都下调了 miR-100 的表达。然而,miR-100 在肝细胞癌 (HCC) 中的表达和功能仍不清楚。本研究旨在检测 miR-100 在 HCC 组织中的表达,并探讨其临床病理和预后意义。同时,分析了 miR-100 对 HCC 细胞生长和凋亡的影响及其潜在的分子机制。结果表明,miR-100 在 HCC 组织中的表达水平明显低于配对的非癌性肝组织。此外,低 miR-100 表达与 HCC 患者肿瘤分级较高、淋巴结转移发生率较高、TNM 分期较晚和肿瘤复发率较高显著相关。多变量生存分析表明,低 miR-100 表达是 HCC 患者的独立预后因素 (HR=1.66,95%CI 1.32-2.82,P=0.019)。此外,我们发现上调 miR-100 通过下调 Polo 样激酶 1 (plk1) 可以抑制 HCC 细胞的生长并增加其凋亡。在 HCC 组织中,miR-100 的表达与 plk1 蛋白的表达呈负相关(r=-0.418;P=0.029)。因此,miR-100 的下调与 HCC 患者进行性病理特征和不良预后相关,miR-100 可以通过靶向 plk1 发挥肿瘤抑制作用。miR-100 可能成为 HCC 的预后标志物和分子治疗靶点。