CUL4B enhances the malignant phenotype of esophageal squamous cell carcinoma by suppressing TGFBR3 expression.

Cullin 4B (CUL4B), which acts as a scaffold protein in CUL4B-RING ubiquitin ligase complexes (CRL4B), is frequently overexpressed in cancer and represses tumor suppressors through epigenetic mechanisms. However, the expression and function of CUL4B in esophageal squamous cell carcinoma (ESCC) have not been well illustrated. In this study, we show that upregulation of CUL4B in ESCC cells enhances proliferation, invasion and cisplatin (CDDP)-resistance, while knockdown of CUL4B significantly represses the malignant activities. Mechanistically, we demonstrate that CUL4B promotes proliferation and migration of ESCC cells through inhibiting expression of transforming growth factor beta receptor III (TGFBR3). CRL4B complex binds to the promoter of TGFBR3, and represses its transcription by catalyzing monoubiquitination at H2AK119 and coordinating with PRC2 and HDAC complexes. Taken together, our findings establish a critical role for the CUL4B/TGFBR3 axis in the regulation of ESCC malignancy.

Long noncoding RNA Ftx regulates the protein expression profile in HCT116 human colon cancer cells.

BACKGROUND: The long noncoding RNA (lncRNA) five prime to Xist (Ftx) is involved in distant metastasis in colorectal cancer (CRC). This study aimed to investigate Ftx alteration-induced proteomic changes in the highly metastatic CRC cell line HCT116. METHODS: Tandem mass tag (TMT)-based proteomics analysis was performed to detect the differential protein expression in Ftx-overexpressing and Ftx-silenced HCT116 cells. The differentially expressed proteins were classified and characterized by bioinformatics analyses, including gene ontology (GO) annotation, GO/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway/protein domain enrichment analyses, as well as hierarchical clustering. A total of 5471 proteins were quantified, and the proteins with |fold change|≥ 1.2 and p < 0.05 were identified as differentially expressed proteins in response to Ftx overexpression or silencing. RESULTS: The bioinformatics analyses revealed that the differentially expressed proteins were involved in a wide range of GO terms and KEGG signaling pathways and contained multiple protein domains. These terms, pathways, and protein domains were associated with tumorigenesis and metastasis in CRC. CONCLUSIONS: Our results indicate that the alteration of Ftx expression induces proteomic changes in highly metastatic HCT116 cells, suggesting that Ftx and its downstream molecules and signaling pathways could be potential diagnostic biomarkers and therapeutic targets for metastatic CRC.

HBeAg mediates inflammatory functions of macrophages by TLR2 contributing to hepatic fibrosis.

BACKGROUND: We and others have confirmed activation of macrophages plays a critical role in liver injury and fibrogenesis during HBV infection. And we have also proved HBeAg can obviously induce the production of macrophage inflammatory cytokines compared with HBsAg and HBcAg. However, the receptor and functional domain of HBeAg in macrophage activation and its effects and mechanisms on hepatic fibrosis remain elusive. METHODS: The potentially direct binding receptors of HBeAg were screened and verified by Co-IP assay. Meanwhile, the function domain and accessible peptides of HBeAg for macrophage activation were analyzed by prediction of surface accessible peptide, construction, and synthesis of truncated fragments. Furthermore, effects and mechanisms of the activation of hepatic stellate cells induced by HBeAg-treated macrophages were investigated by Transwell, CCK-8, Gel contraction assay, Phospho Explorer antibody microarray, and Luminex assay. Finally, the effect of HBeAg in hepatic inflammation and fibrosis was evaluated in both human and murine tissues by immunohistochemistry, immunofluorescence, ELISA, and detection of liver enzymes. RESULTS: Herein, we verified TLR-2 was the direct binding receptor of HBeAg. Meanwhile, C-terminal peptide (122-143 aa.) of core domain in HBeAg was critical for macrophage activation. But arginine-rich domain of HBcAg hided this function, although HBcAg and HBeAg shared the same core domain. Furthermore, HBeAg promoted the proliferation, motility, and contraction of hepatic stellate cells (HSCs) in a macrophage-dependent manner, but not alone. PI3K-AKT-mTOR and p38 MAPK signaling pathway were responsible for motility phenotype of HSCs, while the Smad-dependent TGF-ß signaling pathway for proliferation and contraction of them. Additionally, multiple chemokines and cytokines, such as CCL2, CCL5, CXCL10, and TNF-α, might be key mediators of HSC activation. Consistently, HBeAg induced transient inflammation response and promoted early fibrogenesis via TLR-2 in mice. Finally, clinical investigations suggested that the level of HBeAg is associated with inflammation and fibrosis degrees in patients infected with HBV. CONCLUSIONS: HBeAg activated macrophages via the TLR-2/NF-κB signal pathway and further exacerbated hepatic fibrosis by facilitating motility, proliferation, and contraction of HSCs with the help of macrophages.

Derivation and validation of prognostic models for predicting survival outcomes in Acute-on-chronic liver failure patients.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with high bacterial infection (BI) and short-term mortality. However, many ACLF prognostic predictive modelsare complicated. The aim of this study is to develop prognostic models for ACLF patients to predict BI and mortality. We retrospective recruited 263 patients with ACLF from Shandong Provincial Hospital and Taizhou Enze Medical Center (Group) Enze Hospital. ACLF was defined according to the Asian Pacific Association for the Study of the Liver (APASL) criteria. Multivariable logistic regression was used to derive prediction models for occurring BI and 28-day mortality in ACLF patients. Ninety seven of 263 patients (37%) occurred BI and 41 of 155 (26%) died within 28 days of admission. C-reactive protein (CRP), glucose, and albumin were the independent predictors for occurring BI during the hospital stay. We also found that hepatic encephalopathy (HE), prothrombin time, activated partial thromboplastin time (APRI), and glucose were the independent predictors of 28-day mortality of ACLF patients. Using logistic regression model, we generated a new modified MELD model (M-MELD) by incorporating HE, APRI, and glucose. AUC of M-MELD model was 0.871, which were significantly higher than MELD score (AUC:0.734), MELD-Na score (AUC:0.742), and integrated MELD score (iMELD) (AUC:0.761). HE, MELD score, APRI, and blood glucose were independent risk factors for 28-day mortality of ACLF patients. The modified MELD model (M-MELD) by incorporating HE, APRI, and glucose has better discriminative performances compared with MELD in predicting 28-day mortality.

Microwave ablation versus radiofrequency ablation for perivascular hepatocellular carcinoma: a propensity score analysis.

BACKGROUND: To compare the efficacy and safety of microwave ablation (MWA) and radiofrequency ablation (RFA) as first-line treatments for perivascular HCC. METHODS: This multicentre study enrolled 170 patients with perivascular HCC who underwent MWA or RFA. The ablation response, progression-free survival (PFS), overall survival (OS), and complications between the treatment groups for the total and propensity score-matched (PSM) cohorts were compared. RESULTS: The disease control rates for MWA and RFA were similar in total (94% vs. 91%, p = 0.492) and PSM (93% vs. 93%, p = 1.00) cohorts. The PFS rates at 1, 3, and 5 years were 71%, 55% and 52% in MWA group and 61%, 33% and 28% in RFA group (p = 0.017). The OS rates were comparable between two groups in total (p = 0.249) and PSM cohorts (p = 0.345). In subgroup analyses, the PFS of patients with periportal HCC (45 vs. 36 months, p = 0.048) and a single HCC nodule (51 vs. 42 months, p = 0.014) were significantly better in MWA group than RFA. Major complications were more frequent in the MWA group than in RFA (27% vs. 7%, p < 0.001). CONCLUSION: Compared with RFA, MWA provides better control of tumour progression especially in periportal HCC or single-nodule perivascular HCC patients.

The functions and targets of miR-212 as a potential biomarker of cancer diagnosis and therapy.

Cancer is a major health problem worldwide. An increasing number of researchers are studying the diagnosis, therapy and mechanisms underlying the development and progression of cancer. The study of noncoding RNA has attracted a lot of attention in recent years. It was found that frequent alterations of miRNA expression not only have various functions in cancer but also that miRNAs can act as clinical markers of diagnosis, stage and progression of cancer. MiR-212 is an important example of miRNAs involved in cancer. According to recent studies, miR-212 may serve as an oncogene or tumour suppressor by influencing different targets or pathways during the oncogenesis and the development and metastasis of cancer. Its deregulation may serve as a marker for the diagnosis or prognosis of cancer. In addition, it was recently reported that miR-212 was related to the sensitivity or resistance of cancer cells to chemotherapy or radiotherapy. Here, we summarize the current understanding of miR-212 functions in cancer by describing the relevant signalling pathways and targets. The role of miR-212 as a biomarker and its therapeutic potential in cancer is also described. The aim of this review was to identify new methods for the diagnosis and treatment of human cancers.

Negative feedback loop of ERK/CREB/miR-212-3p inhibits HBeAg-induced macrophage activation.

The activation of liver macrophages is closely related to liver injury after HBV infection. Our previous results demonstrated that HBeAg played a key role in inducing macrophage activation. As we all know, miRNAs are involved in the regulation of multiple immune cell functions. Meanwhile, we have shown that miR-155 positively regulates HBeAg-induced macrophage activation and accelerates liver injury. Subsequently, based on our previous miRNA sequencing results, we further evaluated the role of miR-212-3p called 'neurimmiR' in HBeAg-induced macrophages in this study. First, miR-212-3p expression was significantly elevated in HBeAg-treated macrophages. Meanwhile, we found up-regulation of miR-212-3p significantly decreased the production of cytokines, whereas knockdown of miR-212-3p held the opposite effect by gains and losses of function. Mechanically, although MAPK signal pathway, including ERK, JNK and p38, was activated in HBeAg-induced macrophages, only ERK promoted the expression of miR-212-3p via transcription factor CREB, which was able to bind to the promoter of miR-212-3p verified by ChIP assay. Moreover, we further indicated that up-regulated miR-212-3p inhibited HBeAg-induced inflammatory cytokine production through targeting MAPK1. In conclusion, miR-212-3p was augmented in HBeAg-stimulated macrophages via ERK/CREB signal pathway and the elevated miR-212-3p suppressed inflammatory cytokine production induced by HBeAg through targeting MAPK1.

Radiofrequency ablation versus repeat resection for recurrent hepatocellular carcinoma (≤ 5 cm) after initial curative resection.

OBJECTIVES: Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection, but the management of recurrent HCC remains unclear. To compare the efficacy and safety of radiofrequency ablation (RFA) and repeat resection as the first-line treatment in recurrent HCC. METHODS: This multicenter retrospective study analyzed 290 patients who underwent RFA (n = 199) or repeat resection (n = 91) between January 2006 and December 2016 for locally recurrent HCC (≤ 5 cm) following primary resection. We compared the overall survival (OS), progression-free survival (PFS), and complications between the two treatment groups for the total cohort and the propensity score matched (PSM) cohort. RESULTS: The 1-, 3-, and 5-year OS (90.7%, 69.04%, 55.6% vs. 87.7%, 62.9%, 38.1%, p = 0.11) and PFS (56.5%, 27.9%, 14.6% vs. 50.2%, 21.9%, 19.2%, p = 0.80) were similar in the RFA group and the repeat resection group. However, RFA was superior to repeat resection in complication rate and hospital stay (p ≤ 0.001). We observed similar findings in the PSM cohort of 48 pairs of patients and when OS and PFS were measured from the time of the primary resection. The OS of the RFA group was significantly better than repeat resection group among those with 2 or 3 recurrent tumor nodules in both the total cohort (p = 0.009) and the PSM cohort (p = 0.018). CONCLUSION: RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications. RFA is more efficient and safer than repeat resection in patients with 2 or 3 recurrent tumor nodules. KEY POINTS: • Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection. • RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications. • RFA may be preferred for those with 2 or 3 recurrent HCC nodules.

LncRNA PAPAS promotes hepatocellular carcinoma by interacting with miR-188-5p.

It has been observed that long noncoding RNA (lncRNA) PAPAS regulates rRNA synthesis, but its role in human diseases is unclear. Our study was carried out to investigate the role of PAPAS in hepatocellular carcinoma (HCC). In the present study, we found that PAPAS was upregulated both in plasma from patients with HCC and tumors compared with plasma from healthy people and tumor-adjacent healthy tissues. Expression levels of PAPAS in tumor tissues and plasma of patients with HCC were significantly and positively correlated. Plasma levels of PAPAS effectively distinguished stage I patients from healthy controls. MicroRNA (miR)-188-5p was downregulated in tumor tissues than in tumor-adjacent healthy tissues of patients with HCC, and was inversely correlated with PAPAS in tumor tissues but not in adjacent healthy tissues. PAPAS and miR-188-5p downregulated each other. PAPAS overexpression promoted, while miR-188-5p overexpression inhibited the HCC cell proliferation. Rescue experiment showed that miR-34a overexpression attenuated the effects of PAPAS overexpression. However, PAPAS overexpression failed to affect significantly cancer cell migration and invasion. Therefore, lncRNA PAPAS promotes HCC by interacting with miR-188-5p.

The value of DNA image cytometry combined with brush routine cytology in diagnosing indeterminate biliary strictures: A large sample size retrospective study.

BACKGROUND AND AIM: Brush cytology is widely applied to diagnosis indeterminate biliary stricture but suffer from low sensitivity. Changes in DNA content are a character of malignant cell and can be detected by DNA image cytometry (DNA-ICM). The study aimed to estimate the value of routine cytology (RC), DNA-ICM, and their combination in diagnosing indeterminate biliary strictures. METHODS: A total of 362 patients who underwent both RC and DNA-ICM tests were analysed. Their results were retrospectively applied to final diagnoses. Diagnostic values were compared among RC, DNA-ICM, and their combination based on the location of strictures. RESULTS: The DNA-ICM and combination of two methods had higher diagnostic accuracy than RC in all strictures (63.3% vs 42.3%, P < 0.001, 64.36% vs 42.3%, P < 0.001) and in distal strictures (65.36% vs 42.81%, P < 0.001, 66.01% vs 42.81%, P < 0.001). But in proximal strictures, DNA-ICM showed no superior (51.8% vs 42.81%, P = 0.184). Combination of two methods was not fully significant superior to RC in proximal strictures (55.36% vs 39.29%, P = 0.089). After classification of "suspicious for malignancy" as positive for malignancy, the diagnostic accuracy of DNA-ICM was still higher than that of RC in all strictures (63.3% vs 51.9%, P = 0.002) and in distal strictures (65.36% vs 52.29%, P = 0.001). Combination of two methods was no superior to DNA-ICM alone (64.36% vs 63.3%, P = 0.757). The utilization of DNA-ICM was more accurate in distal strictures than in proximal strictures (65.36% vs 51.8%, P = 0.017). CONCLUSION: DNA-ICM is an objective and effective addition tool with RC, especially in distal strictures. The combination of DNA-ICM and RC showed no superior to DNA-ICM alone but could improve diagnostic accuracy to RC in proximal strictures although not fully significant.

HBeAg induces the expression of macrophage miR-155 to accelerate liver injury via promoting production of inflammatory cytokines.

Activation of Kupffer cells (KCs) induced that inflammatory cytokine production plays a central role in the pathogenesis of HBV infection. The previous studies from our and other laboratory demonstrated miRNAs can regulate TLR-inducing inflammatory responses to macrophage. However, the involvement of miRNAs in HBV-associated antigen-induced macrophage activation is still not thoroughly understood. Here, we evaluated the effects and mechanisms of miR-155 in HBV-associated antigen-induced macrophage activation. First, co-culture assay of HepG2 or HepG2.2.15 cells and RAW264.7 macrophages showed that HepG2.2.15 cells could significantly promote macrophages to produce inflammatory cytokines. Furthermore, we, respectively, stimulated RAW264.7 macrophages, mouse primary peritoneal macrophages, or healthy human peripheral blood monocytes with HBV-associated antigens, including HBcAg, HBeAg, and HBsAg, and found that only HBeAg could steadily enhance the production of inflammatory cytokines in these cells. Subsequently, miRNAs sequencing presented the up- or down-regulated expression of multiple miRNAs in HBeAg-stimulated RAW264.7 cells. In addition, we verified the expression of miR-155 and its precursors BIC gene with q-PCR in the system of co-culture or HBeAg-stimulated macrophages. Meanwhile, the increased miR-155 expression was positively correlation with serum ALT, AST, and HBeAg levels in AHB patients. Although MAPK, PI3K, and NF-κB signal pathways were all activated during HBeAg treatment, only PI3K and NF-κB pathways were involved in miR-155 expression induced by HBeAg stimulation. Consistently, miR-155 over-expression inhibited production of inflammatory cytokines, which could be reversed by knocking down miR-155. Moreover, we demonstrated that miR-155 regulated HBeAg-induced cytokine production by targeting BCL-6, SHIP-1, and SOCS-1. In conclusion, our data revealed that HBeAg augments the expression of miR-155 in macrophages via PI3K and NF-κB signal pathway and the increased miR-155 promotes HBeAg-induced inflammatory cytokine production by inhibiting the expression of BCL-6, SHIP-1, and SOCS-1.

As an independent prognostic factor, USP6 promotes the invasion and metastasis of colon cancer.

The lack of efficient tumor invasion and metastatic biomarkers led to high mortality rates in colon cancer patients. Aberrant expression of ubiquitin-specific protease 6 (USP6) was involved in several diseases including cancer, while its role in the progression of colon cancer was still unclear. In this study, USP6 was evaluated at both mRNA and protein levels by using RT-PCR, western blot and immunohistochemistry staining analyses. The results revealed that high USP6 expression predicted poor disease-specific survival and overall survival through Kaplan-Meier analyses with log-rank tests, univariate and multivariate Cox analyses. Furthermore, cell function assay demonstrated that USP6 could promote colon cancer cells' invasion in vitro and liver metastasis in vivo. These findings indicated that high USP6 expression contributed to the progression of colon cancer and USP6 may be a valuable prognostic factor in patients with colon cancer.

VX-680 induces p53-mediated apoptosis in human cholangiocarcinoma cells.

VX-680 is one selective small-molecule inhibitor of the Aurora kinases. It has been shown to disrupt motosis and induce apoptosis in a wide variety of tumor cell lines. However, its effect on human cholangiocarcinoma (CCA) cells remains uncharacterized. In the current study, we observed the effects of VX-680 on the human CCA (QBC939 and HCCC-9810) cell line. In cell culture, VX-680 inhibited proliferation and induced apoptosis of tumor cell growth in a dose-dependent and time-dependent manner, and exerted the most effective cytotoxicity against HCCC-9810 cells. The proliferation inhibition rate increased from 5.39 to 51.74%, whereas the apoptosis rate increased from 9.59 to 50.02% when HCCC-9810 cells were cultured with 5 µmol/l VX-680 for 48 h. Immunoblot analysis showed that the expression of phospho-p53(Ser-15) was upregulated after 48 h treatment of the cancer cells with VX-680. This activation in p53 was associated with a decrease in Bcl-2 and an increase in Bax, which led to the expression of its downstream effectors (caspase-9 and caspase-3). We further found that pifithrin-α, a p53 inhibitor, attenuated the anticancer effects of VX-680 and downregulated the expression of apotosis-related proteins (Bax and caspase-9). These results suggest that VX-680 could mediate cell death by acting on a P53/Bax/ caspase-3-dependent pathway in human CCA cells.

Overexpression of the metastasis-associated gene MTA3 correlates with tumor progression and poor prognosis in hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers in the world. However, there remains a lack of effective diagnostic and treatment markers. We aimed to explore metastasis-associated protein 3 (MTA3) expression and function in HCC and its relationship with clinicopathological factors. METHODS: We investigated the expression pattern and clinicopathological significance of MTA3 in 90 patients with HCC via immunohistochemistry and explored MTA3 function via gene knockdown of MTA3. RESULTS: MTA3 was overexpressed in HCC cell nuclei and downregulated in HCC cell cytoplasm. The former finding correlated with metastasis (P = 0.010) and poor prognosis (P = 0.018). In addition, deleting MTA3 inhibited HCC cell growth, invasion, and metastasis in vitro, as shown in the colony formation, migration, and wound-healing assays. CONCLUSIONS: These results indicate that MTA3 is an oncogene of HCC, predicts poor prognosis of HCC, and may be a future marker of HCC treatment.

Primary breast cancer induces pulmonary vascular hyperpermeability and promotes metastasis via the VEGF-PKC pathway.

The lung is one of the most frequent target organs for breast cancer metastasis. When breast cancer cells from a primary tumor do not colonize the lung, which we named the premetastatic phase, the microenvironment of the lung has already been influenced by the primary tumor. However, little is known about the exact premetastatic alteration and regulatory mechanisms of the lung. Here, we used 4T1 cells (a mouse breast cancer cell line which can specifically metastasize to the lung) to build a mouse breast cancer model. We found that primary breast tumor induced increased pulmonary vascular permeability in the premetastatic phase, which facilitated the leakage of rhodamine-dextran and the extravasation of intravenous therapy injected cancer cells. Furthermore, tight junctions (TJs) were disrupted, and the expression of zonula occludens-1(ZO-1), one of the most important components of tight junctions, was decreased in the premetastatic lung. In addition, elevated serum vascular endothelial growth factor (VEGF) was involved in the destabilization of tight junctions and the VEGF antagonist bevacizumab reversed the primary tumor-induced vascular hyperpermeability. Moreover, activation of the protein kinase C (PKC) pathway disrupted the integrity of TJs and accordingly, the disruption could be alleviated by blocking VEGF. Taken together, these data demonstrate that primary breast cancer may induce tight junction disruptions in the premetastatic lung via the VEGF-PKC pathway and promote pulmonary vascular hyperpermeability before metastasis. © 2015 Wiley Periodicals, Inc.

Submucosal tunneling endoscopic resection for tumors of the esophagogastric junction.

BACKGROUND: For submucosal tumors (SMTs) originating from the muscularis propria (MP) layer of the esophagogastric junction (EGJ), submucosal tunneling endoscopic resection (STER) is now widely used, and it shows promise in overcoming the limitations of endoscopic submucosal dissection. AIMS: This study aimed to evaluate the efficacy and safety of the STER technique for treating SMTs of the EGJ originating from the MP layer. MATERIAL AND METHODS: From October 2011 to February 2014, 20 patients were enrolled for STER surgery. RESULTS: The patients were categorized into three groups according to the tumor location. The esophagocardiac group had a lower complication rate (0/7) compared with the cardiac group (3/6) and the gastrocardiac group (3/7). The mean operation time in the esophagocardiac (83 ± 24 min) and cardiac (83 ± 55 min) groups was significantly shorter than that of the gastrocardiac group (145 ± 44 min) (P < 0.05). The en bloc resection rate was 100%, with no severe complications and no recurrence during the follow-up period. CONCLUSIONS: The STER technique appears to be a feasible and safe minimally invasive approach for SMTs originating from the MP layer of the EGJ, with satisfying en bloc resection, a short operation time, and low rates of severe complications.

VEGFR-1 activation-induced MMP-9-dependent invasion in hepatocellular carcinoma.

AIM: VEGFR-1 can promote invasion through epithelial-mesenchymal transition induction in hepatocellular carcinoma (HCC). This study aims to elucidate VEGFR-1 impact on proteolytic enzymes profile involved with invasion. MATERIALS & METHODS: The effect on cell invasion was evaluated by invasive and migration assays with and without VEGFR-1 activation. The mechanism was investigated by real-time PCR, western blot and gelatin zymography using inhibitors for MMP-9. In total, 95 HCC patients were enrolled for its clinical value evaluation. RESULTS: VEGFR-1 activation induced invasion in HCC cells with an increase in the expression and activity of MMP-9 and Snail. MMP-9 blockage effectively inhibited VEGFR-1-induced invasion. High coexpression of both in HCC predicted a worse clinical outcome. CONCLUSION: Data show a novel VEGFR-1 activation-to-MMP-9 mechanism promoting HCC invasion.

MicroRNAs as a novel class of diagnostic biomarkers in detection of hepatocellular carcinoma: a meta-analysis.

MicroRNAs (miRNAs) have been proposed as promising diagnostic biomarkers for many diseases, particularly in the field of cancer research. Numerous studies have explored the use of miRNAs in the detection of hepatocellular carcinoma (HCC), with some reporting inconsistent results. Thus, we conducted this meta-analysis to evaluate the potential diagnostic value of miRNAs in HCC. All relevant literature was collected from the PubMed and other databases before June 3, 2014. The summary receiver operator characteristic (SROC) curve and other parameters were used to estimate overall predictive performance. Fourteen studies involving 1,848 cases with HCC and 1,187 controls (576 healthy controls and 611 individuals with chronic liver diseases) were included in this meta-analysis. SROC analyses for the diagnostic power of miRNAs yielded an area under the curve (AUC) of 0.93 with 86 % sensitivity and 86 % specificity in discriminating patients with HCC from healthy subjects and an AUC of 0.88 with 79 % sensitivity and 83 % specificity in differentiating patients with HCC from those with chronic liver diseases (CLDs). Furthermore, subgroup analyses showed that miRNA panels yielded excellent diagnostic characteristics, with an AUC of 0.99 (96 % sensitivity and 96 % specificity) for detection of HCC from healthy controls and an AUC of 0.93 (85 % sensitivity and 88 % specificity) for HCC from those with CLDs. MiRNAs might be novel potential biomarkers for the diagnosis of HCC, and a combination of multiple miRNAs could significantly improve the diagnostic accuracy.