Abstract
BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies with a high morbidity and mortality worldwide. MicroRNAs are key regulators of HCC genesis. However, the regulatory role and underlying mechanisms of microRNA in HCC is still limited.MethodsCyclin B1 (CCNB1) mRNA levels were examined in non-tumor and liver cancer of The Cancer Genome Atlas (TCGA) cohort. CCNB1 was knockdown to evaluate the HCC cell proliferation, migration and invasion. MicroRNA-144 targeting CCNB1 was identified with TargetScan analysis and confirmed with reporter assay. Overexpression of MicroRNA-144 was achieved using microRNA mimics and function of microRNA-144 was tested in vitro HCC cell line proliferation and in vivo tumor formation experiments.ResultsHere, we found that the high level expression of CCNB1 was closely associated with poor prognosis in HCC patients. Knockdown of CCNB1 by RNA interference significantly inhibited cell proliferation, migration and invasion in HCC. Furthermore, we found that miR-144 directly targeted CCNB1 and inhibited CCNB1 expression. Moreover, in vivo experiments of subcutaneous tumor formation further demonstrated that miR-144 delayed tumor formation by negative regulation of CCNB1.ConclusionTherefore, we conclude that microRNA-144/CCNB1 axis plays an important role in human HCC. Therapies targeting microRNA-144 could potentially improve HCC treatment.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high morbidity and mortality worldwide
Bioinformatics analysis of Cyclin B1 (CCNB1) expression in HCC tissues and normal liver tissue CCNB1 was reported highly expressed in several different human cancers [15]
To study CCNB1 in HCC, we first analyzed mRNA expression in HCC tissues and normal liver tissues based on the liver cancer gene expression profiles in the The Cancer Genome Atlas (TCGA) database
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high morbidity and mortality worldwide. MicroRNAs are key regulators of HCC genesis. The regulatory role and underlying mechanisms of microRNA in HCC is still limited. The precision pathogenesis of HCC is unclear and the effective prevention and treatment are still lacking. Studying the molecular mechanism of HCC proliferation and metastasis, accurately predicting prognosis for patients, preventing HCC metastasis, and taking effectively preventive measures could be a breakthrough to improve the efficacy of prognosis and treatment. CCNB1 has been demonstrated to have significant predictive power in overall survival of ER+ breast cancer patients and HBV-related HCC recurrence [9, 10]. The detailed functions of CCNB1 in HCC and how CCNB1 is regulated are still remaining elusive
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