miR-133a-3p Regulates Hepatocellular Carcinoma Progression Through Targeting CORO1C.

INTRODUCTION: MicroRNAs (miRNAs) are key modulators for gene expression via inducing translational repression or target gene degradation. miR-133a-3p was reported to stimulate or inhibit cancer progression but its role in hepatocellular carcinoma (HCC) remains to be explored. METHODS: Quantitative real-time PCR (RT-qPCR) was utilized to explore miR-133a-3p expression level in HCC cells. Dual-luciferase activity reporter assay was used to validate the direct interaction between miR-133a-3p and coronin-like actin-binding protein 1C (CORO1C). In addition, we analyzed the expression levels of miR-133a-3p and CORO1C in HCC tissues and normal tissues on the UCALAN website. Functional assays including cell counting kit-8 assay, colony formation assay, flow cytometry analysis and transwell invasion assay were conducted to explore the biological functions of miR-133a-3p in HCC. RESULTS: miR-133a-3p was found to have downregulated expression in HCC tissues and cells. Meanwhile, we showed that low miR-133a-3p levels were correlated with poorer overall survival of HCC patients. Overexpression of miR-133a-3p suppressed HCC cell growth and invasion but promoted cell apoptosis via targeting CORO1C. DISCUSSION: Our results revealed a novel mechanism of miR-133a-3p in regulating HCC progression and provided evidence that miR-133a-3p functions as a tumor suppressor in HCC.

Downregulation of serum exosomal miR-320d predicts poor prognosis in hepatocellular carcinoma.

BACKGROUND: MicroRNAs (miRNAs) is a class of functional regulator of tumorigenesis of human cancer including hepatocellular carcinoma (HCC). However, the potential clinical significance of serum exosomal miR-320d in HCC has not been elucidated. METHODS: Real-time reverse transcription PCR was used to detect the expression pattern of serum exosomal miR-320d in patients with HCC, and the correlation between the deregulation of serum exosomal miR-320d and the clinical outcome of HCC was explored. The biological function of exosomal miR-320d in HCC was also investigated. RESULTS: Our results showed that the expression levels of exosomal miR-320d were remarkably reduced in the serum samples of HCC patients and the culture medium of HCC cell lines compared with their respective controls. Serum exosomal miR-320d could differentiate the HCC patients from healthy controls with high accuracy. In addition, its level was remarkably increased in the HCC patients who had received surgical treatment. Moreover, reduced serum exosomal miR-320d was associated with advanced tumor stage, positive lymph node metastasis, and poorly differentiated tumors. HCC patients with lower serum exosomal miR-320d had shorter overall and disease-free survival. Low serum exosomal miR-320d was identified to be an independent unfavorable prognostic factor for HCC. Finally, overexpression of miR-320d inhibited the proliferation and invasion of HCC cells, and BMI1 was demonstrated to be a direct target of miR-320d. CONCLUSION: Taken together, serum exosomal miR-320d could be a potential non-invasive biomarker for the diagnosis and prognosis of HCC.

The association between UGT1A7 polymorphism and cancer risk: a meta-analysis.

BACKGROUND: studies investigating the associations between UDP-glucuronosyltransferase 1A7 (UGT1A7) gene polymorphisms and various carcinomas risk reported conflicting results. To derive a more precise estimation of the association, we have conducted a meta-analysis. METHODS: data were collected from the following electronic databases: PubMed, Medline and Chinese Biomedical Literature Database, with the last report up to September 2011. Case-control studies containing available genotype frequencies of UGT1A7 were chose. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of association. RESULTS: a total of 22 separate case-control studies including 3852 cases and 5604 controls based on the search criteria were involved in this meta-analysis. The combined results based on all studies showed that there was a statistically significant link between UGT1A7*3 allele and cancer risk (OR = 1.31, 95%CI = 1.14-1.50, P = 0.0001). In the stratified analysis by racial descent, significant increased risk was found in Asian population for UGT1A7*3 allele (OR = 1.41, 95%CI = 1.22-1.63, P < 0.00001). No significant associations were found between the UGT1A7 polymorphism and cancer susceptibility among Caucasians and African-Americans. In the subgroup analysis by cancer types, significant associations were found in UGT1A7*2 allele (OR = 1.23, 95%CI = 1.06-1.43, P = 0.006) and *3 allele (OR = 1.51, 95%CI = 1.11-2.06, P = 0.009) for hepatocellular carcinoma, *3 allele for lung cancer (OR = 1.36, 95%CI = 1.11-1.68, P = 0.004) and for bladder cancer (OR = 1.50, 95%CI = 1.09-2.07, P = 0.01). CONCLUSIONS: This meta-analysis suggests that the UGT1A7*3 allele is a risk factor for cancer among Asians, especially for hepatocellular carcinoma.