Abstract
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.
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Thanks to the sincere help and technical support by the department of biochemistry and molecular biology in Xi’an Jiao Tong University.
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P. Chen and X. Zhao should be regarded as joint first authors for their equal contributions.
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Chen, P., Zhao, X. & Ma, L. Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. Mol Cell Biochem 383, 49–58 (2013). https://doi.org/10.1007/s11010-013-1753-0
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DOI: https://doi.org/10.1007/s11010-013-1753-0