Exosomal miRNAs are proposed as excellent candidate biomarkers for clinical applications. However, little is known about their potential roles as prognostic biomarkers in lung cancer. In this study, we explored the prognostic value of plasma exosomal microRNAs (miRNAs) for non-small-cell lung cancer (NSCLC). Using a quantitative polymerase chain reaction (qPCR) array panel, we analyzed 84 plasma exosomal miRNAs in 10 lung adenocarcinoma patients and 10 matched healthy controls. The qPCR array showed 30 aberrantly expressed exosomal miRNAs. Nine candidate miRNAs were selected based on differential expression and previous reports for further evaluating their prognostic roles in 196 NSCLC patients. Elevated levels of exosomal miR-23b-3p, miR-10b-5p and miR-21-5p were independently associated with poor overall survival (with hazard ratio [95% confidence interval]: 2.42 (1.45 - 4.04), P = 0.001; 2.22 (1.18 - 4.16), P = 0.013; 2.12 (1.28 - 3.49), P = 0.003, respectively). When compared to the clinical prognostic variables only model, adding the three exosomal miRNA signatures significantly improved survival predictive accuracy with an increase of time-dependent area under the receiver operating characteristic curve from 0.88 to 0.91 (P=0.015). Our results indicated that plasma exosomal miR-23b-3p, miR-10b-5p and miR-21-5p are promising non-invasive prognostic biomarkers of NSCLC.

BackgroundHepatocellular carcinoma (HCC) is third leading cause of cancer-related death globally. Evidence suggest that long non-coding RNAs (lncRNAs) have emerged as key regulators of tumorigenesis and metastasis in HCC. In this study, we investigated the functional significance of SNHG12 and explored whether SNHG12 can directly interact with miR-199a/b-5p in the progression of HCC.MethodsWe determined the expression level of SNHG12 in HCC tissues with quantitative real-time PCR and then studied its clinical significance. The binding site between SNHG12 and miR-199a/b-5p was confirmed using dual luciferase assay and RNA immunoprecipitation (RIP) assay. SNHG12 was silenced through the siRNA transfection to determine whether SNHG12-siRNA is able to affect cell proliferation, invasion and metastasis.ResultsSNHG12 was significantly higher in the HCC tissues than that in the adjacent normal tissues. There were direct interactions between miR-199a/b-5p and the binding site of SNHG12. SNHG12 functioned as an endogenous sponge for miR-199a/b-5p to regulate the expression of MLK3 and affect the NF-κB pathway.ConclusionSNHG12 may serve as a valuable biomarker and a potential therapeutic target for HCC.

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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are key in carcinogenesis. The aim of the present study was to investigate the role of lncRNA GAS5 in HCC tissues and to define the role of growth arrest-specific 5 (GAS5) in the regulation of hepatoma cell proliferation, invasion and apoptosis. Quantitative polymerase chain reaction and in situ hybridization were performed to investigate the expression of GAS5 in tumor tissues and corresponding adjacent tissues from 50 patients with HCC. Low expression of GAS5 was significantly correlated with differentiation (P<0.010) and portal vein tumor thrombosis (P=0.001). Multivariate analysis indicated that GAS5 expression was an independent predictor for overall survival (P=0.017). Further experiments demonstrated that overexpression of GAS5 significantly suppressed the proliferation and invasion of hepatoma cells in vitro. Overexpression of GAS5 significantly promoted the apoptosis of hepatoma cells. In addition, it was demonstrated that GAS5 negatively regulates vimentin expression in vitro and in vivo. Notably, vimentin knockdown promoted GAS5-pcDNA3.1-inhibition of hepatoma cell proliferation. In conclusion, the present study suggests an important role of GAS5 in the molecular etiology of HCC and suggests the potential application of GAS5 in HCC therapy.

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Targeted therapy based on adjustment of microRNA (miRNA)s activity takes great promise due to the ability of these small RNAs to modulate cellular behavior. However, the efficacy of miR-101 replacement therapy to hepatocellular carcinoma (HCC) remains unclear. In the current study, we first observed that plasma levels of miR-101 were significantly lower in distant metastatic HCC patients than in HCCs without distant metastasis, and down-regulation of plasma miR-101 predicted a worse disease-free survival (DFS, P<0.05). In an animal model of HCC, we demonstrated that systemic delivery of lentivirus-mediated miR-101 abrogated HCC growth in the liver, intrahepatic metastasis and distant metastasis to the lung and to the mediastinum, resulting in a dramatic suppression of HCC development and metastasis in mice without toxicity and extending life expectancy. Furthermore, enforced overexpression of miR-101 in HCC cells not only decreased EZH2, COX2 and STMN1, but also directly down-regulated a novel target ROCK2, inhibited Rho/Rac GTPase activation, and blocked HCC cells epithelial-mesenchymal transition (EMT) and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo. These results provide proof-of-concept support for systemic delivery of lentivirus-mediated miR-101 as a powerful anti-HCC therapeutic modality by repressing multiple molecular targets.

More than 1000 candidate-gene association studies on genetic susceptibility to lung cancer have been published over the last two decades but with few consensuses for the likely culprits. We conducted a comprehensive review, meta-analysis and evidence strength evaluation of published candidate-gene association studies in lung cancer up to November 1, 2015. The epidemiological credibility of cumulative evidence was assessed using the Venice criteria. A total of 1018 publications with 2910 genetic variants in 754 different genes or chromosomal loci were eligible for inclusion. Main meta-analyses were performed on 246 variants in 138 different genes. Twenty-two variants from 21 genes (APEX1 rs1130409 and rs1760944, ATM rs664677, AXIN2 rs2240308, CHRNA3 rs6495309, CHRNA5 rs16969968, CLPTM1L rs402710, CXCR2 rs1126579, CYP1A1 rs4646903, CYP2E1 rs6413432, ERCC1 rs11615, ERCC2 rs13181, FGFR4 rs351855, HYKK rs931794, MIR146A rs2910164, MIR196A2 rs11614913, OGG1 rs1052133, PON1 rs662, REV3L rs462779, SOD2 rs4880, TERT rs2736098, and TP53 rs1042522) showed significant associations with lung cancer susceptibility with strong cumulative epidemiological evidence. No significant associations with lung cancer risk were found for other 150 variants in 98 genes; however, seven variants demonstrated strong cumulative evidence. Our findings provided the most updated summary of genetic risk effects on lung cancer and would help inform future research direction.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The biological mechanisms of hepatocarcinogenesis and progression are poorly understood. Experimental models of HCC provide valuable tools to evaluate the risk factors, new treatment modalities and biologic characteristics. Under the constant evolution in model design and technology development, new experimental models continue to emerge, including spontaneous models, induced models, viral models, transplantable models, and genetically engineered models. These models are used as tools to investigate basic biological mechanisms of growth and differentiation, oncogene function, and as systems to test new diagnostic and therapeutic approaches. Each model has its own advantages and disadvantages. The progress in HCC model construction and studies are summarized in this review.