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Nonalcoholic fatty liver disease (NAFLD) is a multifactorial metabolic syndrome which could develop into hepatocellular carcinoma (HCC). Exosomes could mediate intercellular communications and play key roles in the occurrence and development of many diseases including NAFLD and HCC. However, expressions and roles of the genes related to exosomes in NAFLD-related HCC remain unclear. The objective of this study was to investigate the expressions and diagnostic values of exosome-related genes in NAFLD-related HCC. Firstly, we identified 15 genes related to exosome secretion by database searching. Two subgroups of patients with NAFLD-related HCC from GEO database were identified on the basis of exosome-related genes. High level of memory CD4 + T cells and low expressions of Immune Checkpoint genes were observed in the group with highly expressed genes which could promote exosome secretion. Subsequently, the logistic regression analysis was used to generate the formula based on three selected exosome-related genes in NAFLD-related HCC cohort. Receiver operating characteristic (ROC) curve analysis confirmed the good predictive power of formula. Functional analysis showed abundant metabolism-related pathways were screened out in DEGs between the high and low risk-score groups. The risk score from the formula was also positively correlated with memory CD4 + T cells and negatively associated with Immune Checkpoint genes. Finally, prognostic potential of the Exosome-related formula was analyzed in HCC cohort from TCGA database, and patients in the group with highly expressed exosome-promoted genes showed significantly reduced overall survival. We also constructed a nomogram to improve the predictive value of the formula for evaluating the prognosis of patients with HCC. In summary, our study clarified the significance of exosome-related genes in the development of NAFLD-related HCC.

Accumulated studies have shown that low expression of 25-hydroxyvitamin D [25(OH)D] was significantly associated with the risk of non-alcoholic fatty liver disease (NAFLD). However, the exact causality is still unknown. The aim of this study was to investigate whether levels of 25(OH)D are associated with risk of NAFLD, using a two-sample Mendelian randomization (MR).Data from a recent large vitamin D genome-wide association study (GWAS) on 417,580 Europeans were utilized, and the largest published histology-based NAFLD GWAS study (1,483 cases and 17,781 healthy controls) for genetic variants predicted to cause NAFLD were searched. All genetic datasets for the MR analyses were obtained using publicly available summary statistics based on individuals of European ancestry from the MR-Base and NHGRI-EBI GWAS Catalog database. Inverse-variance weighted (IVW) MR approach was used to estimate causal effects in the main analysis, complemented by 4 additional methods to control for pleiotropy. Sensitivity analyses were conducted to verify whether heterogeneity and pleiotropy can bias the MR results.The MR analysis did not provide strong evidence for the causal association of circulating 25(OH)D with NAFLD by IVW method (OR = 0.746, 95%CI 0.517-1.078; P = 0.119). The results were consistent using four other MR methods. Sensitivity analysis using all different analytical approaches yielded similar results. There was no evidence for pleiotropy (MR-Egger intercept: -0.0003758, P = 0.970). The replication process also showed consistent results using IVW method (P = 0.710).This study indicates that serum 25(OH)D levels did not possess an obvious effect on the risk of NAFLD. The associations in previous studies may be due to residual confounding or reverse causation.

Background Multiple studies have demonstrated the involvement of low-density lipoprotein receptor-related protein 5 (LRP5) in metabolism-related diseases. This study explored the relationship between the LRP5 rs556442 gene polymorphism and the risks of non-alcoholic fatty liver disease (NAFLD) and coronary heart disease (CHD) in a Chinese Han population. Methods This retrospective case–control study included 247 patients with NAFLD, 200 patients with CHD, 118 patients with both NAFLD and CHD, and 339 healthy controls from June 2018 to June 2019 at Qingdao Municipal Hospital. Basic information and clinical characteristics were collected for all subjects. The genotype and allele frequency of LRP5 rs556442 were determined. Results The genotype distributions of LRP5 rs556442 differed significantly between the CHD and NAFLD + CHD groups (P LRP5 rs556442 GG genotype markedly promoted the risk of NAFLD in CHD patients [odds ratio (OR) = 2.857, 95% confidence interval (CI): 1.196–6.824, P = 0.018). After adjustment for sex, age, and body mass index (BMI), this association remained significant (OR = 3.252, 95% CI: 1.306–8.102, P = 0.011). In addition, the LRP5 rs556442 AA + AG genotype was associated with an increased BMI in obese NAFLD patients (OR = 1.526, 95% CI: 1.004–2.319, P = 0.048). However, after adjustment for sex and age, this association was no longer significant (OR = 1.504, 95% CI: 0.991–2.282, P = 0.055). Conclusions This study found that the LRP5 rs556442 GG genotype increased the risk of NAFLD in CHD patients and AA + AG genotype may be associated with an increased BMI in obese NAFLD patients among a Chinese Han population. Trial registration ChiCTR, ChiCTR1800015426. Registered 28 March 2018—Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=26239.

Description, DRAM-mediated mechanism participates in lipid-induced exosome secretion from hepatic cells in NAFLD., The biogenesis and diagnostic value of exosomes in nonalcoholic fatty liver disease (NAFLD) are unclear. In this study, we revealed that the plasma exosome level was higher in patients with NAFLD than that in healthy controls. Damage-regulated autophagy modulator (DRAM) was identified as one of the genes related to exosome secretion in patients with NAFLD. Then, loss or knockdown of DRAM down-regulated exosome secretion from hepatic cells using a knockout mouse model and a knockdown cell model. DRAM knockout reversed high-fat diet–induced increase of secreted exosomes. Furthermore, DRAM knockdown inhibited fatty acid (FA)–induced lysosomal membrane permeabilization and lysosome inhibitor reversed the down-regulation of exosome release in DRAM knockout mice. Last, FA-induced DRAM interacted with stomatin and promoted its lysosomal localization to enhance exosome secretion from hepatic cells. We revealed a DRAM-mediated mechanism for exosome secretion and provided the foundation for plasma exosomes as a potential biomarker for NAFLD.

DNA damage-regulated autophagy modulator 1 (DRAM1) could play important roles in inflammation and hepatic apoptosis, while its roles in alcohol-related liver disease (ALD), which is characterized by hepatic inflammation and apoptosis, are still unclear. In this study, we explored the expression, role, and mechanism of DRAM1 in ALD. Firstly, our results showed that DRAM1 was significantly increased in liver tissues of mice at the early stage of alcohol treatment. In addition, DRAM1 knockout reduced, and liver-specific overexpression of DRAM1 aggravated, alcohol-induced hepatic steatosis, injury, and expressions of M1 macrophage markers in mice. Furthermore, ethanol-induced DRAM1 of hepatic cells increased pyruvate kinase M2 (PKM2)-enriched extracellular vesicles (EVs), and ectosomes derived from hepatic cells with DRAM1 overexpression promoted macrophage activation. Mechanistic investigations showed that DRAM1 interacted with PKM2 and increased the PKM2 level in plasma membrane. At last, DRAM1 was significantly increased in liver tissues of ALD patients, and it was positively correlated with M1 macrophage markers. Taken together, this study revealed that ethanol-induced DRAM1 of hepatic cells could increase the PKM2-enriched EVs, promote macrophage activation, and aggravate the disease progression of ALD. These findings suggested that DRAM1 might be a potentially promising target for the therapy of ALD., Graphical Abstract, In this study, ethanol-induced DRAM1 could increase the level of PKM2 in extracellular vesicles released from hepatic cells, promote macrophage activation, and aggravate the progression of alcohol-related liver disease (ALD). These suggested that DRAM1 might be a potential target for the treatment of patients with ALD.

BACKGROUND The aim of this study was to explore the impact of Ras homolog C/Rho-associated coiled-protein kinase (Rho/ROCK) signaling pathways intervention on biological characteristics of the human multiple myeloma cell lines RPMI-8226 and U266 cells, and to investigate the expression of RhoC, ROCK1, and ROCK2 in RPMI-8226 and U266 cells. MATERIAL AND METHODS RPMI8226 and U266 cell lines were treated by 5-aza-2-deoxycytidine (5-Aza-Dc), trichostatin A (TSA), RhoA inhibitor CCG-1423, Rac1 inhibitor NSC23766, and ROCK inhibitor fasudil. Cell proliferation was examined by Cell Counting Kit-8 (CCK-8) assay and clone formation. Cell apoptosis was examined by flow cytometry and TUNEL assay. The mRNA and protein expressions of RhoC, ROCK1, and ROCK2 were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot, respectively. RESULTS CCG-1423, NSC23766, and fasudil could significantly inhibit the proliferation of RPMI8226 and U266 cells. The inhibitory effect was dose- and time-dependent within a certain concentration range (P

Background: MiR-1323 was identified in 2006. Until now, the roles and mechanisms of miR-1323 in the progression of cancers including hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to investigate the expressions, roles and mechanisms of miR-1323 in HCC development. Methods: QRT-PCR was used to evaluate the expressions of miR-1323, GAS5 and TP53INP1 in HCC tissues and cell lines. CCK-8 assay, transwell invasion assay and flow cytometry assay were conducted to evaluate the proliferation, invasion and apoptosis of HCC cells. Luciferase assay was used to identify microRNA-target interaction. Results: Firstly, our results showed that miR-1323 promoted proliferation and invasion, and inhibited apoptosis of HCC cells. Secondly, we found that TP53INP1 was a direct target of miR-1323 and could reverse the effects of miR-1323 on proliferation, invasion and apoptosis of HCC cells. Thirdly, our results showed that long non-coding RNA (lncRNA) GAS5 and miR-1323 could interact with each other and affect biological processes of HCC cells. Furthermore, we identified the negative correlations between miR-1323 and TP53INP1, and between miR-1323 and GAS5 in tumor tissues of patients with HCC. Conclusion: Taken together, our study revealed the important roles of GAS5/miR-1323/TP53INP1 axis in HCC progression. This study also provided promising strategies for targeted therapy of patients with HCC.

Adenylate cyclase 7 (AC7) has been reported to participate in various biological processes during cancer progression. However, the roles of AC7 in all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells are still unknown. In this study, firstly, our results showed that AC7 affected intracellular cAMP level and influenced ATRA-induced differentiation of APL cells. Secondly, we revealed that miR-192 could directly target AC7 expression and knockdown of miR-192 promoted ATRA-induced APL cell differentiation by regulating AC7 expression. Furthermore, we found that AC7 expression was lower in patients with relapsed APL than that in patients with newly diagnosed APL, while miR-192 expression was relatively higher in patients with relapsed APL. Taken together, our results show that miR-192-mediated AC7 could play important roles in differentiation of APL cells, AC7 and miR-192 might be new biomarkers and therapeutic targets for patients with relapsed APL.

Hepatocellular carcinoma (HCC) is one of the most prevalent and malignant tumors with a high mortality rate worldwide. Due to the lack of diagnostic methods with high sensitivity and specificity, the majority of HCC patients are diagnosed at an advanced stage. New biomarkers and antitumor agents need to be explored for the diagnosis and treatment of HCC. The multifunctional transcription factor Yin Yang 1 (YY1) could act as a transcriptional activator or a repressor in the regulation of gene expression. YY1 has been shown to play pivotal roles in proliferation, metastasis, angiogenesis, metabolic disorder, apoptosis, and drug resistance during HCC progression. Recent studies also suggested that YY1 was a crucial transcription factor that interacted with the promoter of target genes to activate oncogenes or inhibit tumor suppressor genes to regulate downstream signaling pathways in HCC cells. Furthermore, many studies showed that YY1 was overexpressed in HCC tissues and high expression of YY1 was associated with poor disease-free survival and overall survival of patients with HCC. In this chapter, we summarized the role, regulatory mechanism, and clinical correlation of YY1 during HCC progression.

The 2019 novel coronavirus disease, SARS-CoV-2, is now spreading globally and is characterized by person-to-person transmission. However, it has recently been found that individuals infected with SARS-CoV-2 can be asymptomatic, and simultaneously a source of infection in others. The viral load detected in nasopharyngeal swabs of asymptomatic carriers is relatively high, with a great potential for transmission. More attention should be paid to the insidious spread of disease and harm contributed by asymptomatic SARS-CoV-2 carriers. To provide a theoretical basis for the accurate and early clinical identification of asymptomatic patients, this review objectively summarizes the epidemic status, transmission characteristics and clinical features of asymptomatic patients with SARS-CoV-2 infection.

Millions of people were infected with the coronavirus disease 2019 (COVID‐19) all over the world. Data on clinical symptoms of pediatric inpatients with COVID‐19 infection were unclear. The aim of study was to investigate the clinical features of pediatric inpatients with SARS‐CoV‐2 infection. PubMed, EMBASE, and the Cochrane Library were searched to seek for studies providing details on pediatric inpatients with SARS‐CoV‐2 infection which were published from 1‐January‐2020 to 21‐April‐2020. Studies with more than 5 pediatric inpatients were included in our meta‐analysis.This study was registered in the PROSPERO database (CRD42020183550). As the results shown, fever (46%) and cough (42%) were the main clinical characters of pediatric inpatients with SARS‐CoV‐2 infection and the other clinical characters such as Diarrhea, Vomiting, Nasal congestion, and Fatigue account for 10% in pediatric inpatients. The proportion of asymptomatic cases was 0.42 (95%CI: 0.27‐0.59) and severe cases was 0.03(95%CI: 0.01‐0.06). For the laboratory result, leukopenia (21%) and lymphocytosis (22%) were the mainly indicators for pediatric inpatients, followed by high aspartate aminotransferase(AST) (19%), lymphopenia (16%), high alanine aminotransferase (ALT) (15%), high C‐reactive protein (CPR) (17%), lymphopenia (16%), leukocytosis (13%), high D‐dimer (12%) and high creatine kinase‐MB (CK‐MB)(5%). Regard to chest imaging features, unilateral and bilateral accounts for 22% in pediatric inpatients, respectively. In conclusion, compared with adult inpatients with SARS‐CoV‐2 infection, the pediatric inpatients had mild clinical characters, lab test indicators, and chest imaging features. More clinical studies focus on the pediatric patients with SARS‐CoV‐2 infection in other countries should be conducted. This article is protected by copyright. All rights reserved.

Background MiRNAs are a group of multifunctional non-coding RNAs which play an important role in the various physiological processes including the development of NAFLD. Recent studies have shown that miR-30b-5p tightly associated with the abnormal lipid metabolism in patients with NAFLD, but the detailed mechanism of miR-30b-5p in the lipid metabolism was remain unclear. The aim of this study was to investigate the effect of miR-30b-5p on the lipid metabolism in hepatocellular carcinoma Huh-7 cells. Material and methods The correlation of intracellular fat content with the expression of miR-30b-5p in Huh-7 cells and HepG2 cells was investigated by treated cells with different concentrations of FFAs. The effect of miR-30b-5p on the lipid deposition in Huh-7 cells was tested by oil red O staining and TG concentrations measurement. qRT-PCR and western blot were used to investigate the lipid metabolism-related genes PPAR-α, SREBP-1, and GULT1 in miR-30b-5p overexpressed or inhibited Huh-7 cells. Target genes of miR-30b-5p were predicted using starBase, miRDB, and TargetScan databases and verified by qRT-PCR and western blot. Results The expression of miR-30b-5p was significant decreased in the FFAs treated Huh-7 cells and HepG2 cells. Overexpressing miR-30b-5p in Huh-7 cells decreased the number and size of lipid droplets and intracellular TG concentrations in Huh-7 cells. Expression of fatty acid oxidation related gene PPAR-α was increased and expression of lipid synthesis related gene SREBP-1 was decreased in the miR-30b-5p overexpressed Huh-7 cells. In addition, miR-30b-5p regulates the intracellular lipid metabolism by targeting PPARGC1A. Conclusions Overexpression of miR-30b-5p could reduce the intracellular fat deposition in Huh-7 cells, and miR-30b-5p might regulate the intracellular lipid metabolism by targeting the PPARGC1A in Huh-7 cells.

Hepatic ischemia-reperfusion injury (IRI) could result in severe liver damage and dysfunction during liver surgery and transplantation. As one of the Interferon (IFN)-stimulated genes, IFIT3 exerted antitumor activity but its roles in hepatic IRI are still unknown. In this study, roles of IFIT3 in hepatic IRI were investigated using a mouse hepatic IRI model and a cellular hypoxia-reoxygenation model. Firstly, our results showed that IFIT3 was up-regulated in reperfused liver tissues of patients undergoing liver transplantation and was positively correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Secondly, knockdown of IFIT3 could significantly ameliorate hepatic IRI and suppress ischemia and reperfusion-induced release of inflammatory cytokines in vivo and in vitro. Furthermore, knockdown of IFIT3 inhibited phosphorylation of STAT1 and STAT2, and decreased expressions of IFN-stimulated genes induced by ischemia and reperfusion in vivo and in vitro. These data highlight the importance and potential clinical use of IFIT3 in hepatic IRI.

Background: Long noncoding ribonucleic acid (lncRNA) X-inactive-specific transcript (Xist) was reported to affect cell proliferation and metastasis in hepatocellular carcinoma (HCC). However, there are rare reports focusing on the diagnostic evaluation and regulatory mechanism of Xist expression from peripheral blood cells of patients with HCC. Methods: In this study, a cohort of 206 female participants including healthy volunteers (HVs) and patients with chronic hepatitis B (CHB), cirrhosis and HCC was recruited. Coculture system was used to evaluate the effects of exosomal JPX transcript, XIST activator (Jpx) on Xist expression of blood cells. Results: First, Xist expressions of both peripheral blood mononuclear cells and granulocytes were upregulated in female patients with HCC, and showed significantly increased discriminatory power when differentiating female patients with early-stage HCC from controls or differentiating female patients with HCC from patients with CHB and cirrhosis, compared with alpha fetoprotein (AFP). Then, another lncRNA Jpx that was an activator of Xist was upregulated in exosomes, mononuclear cells and granulocytes of female patients with HCC. Furthermore, our results showed that Jpx could be delivered from HCC cells to blood cells via exosomes and activate Xist expression of blood cells by repressing the transregulatory effects of CCCTC-binding factor (CTCF). Conclusions: This study revealed an exosome-mediated regulation of Xist expression in blood cells and suggested that Xist expressions of mononuclear cells and granulocytes would be promising biomarkers for diagnosis of female patients with HCC.

YY1 is a DNA-binding transcription factor and reported to be involved in cancer progression. Histone deacetylase inhibitor (HDACi) could inhibit proliferation and promote apoptosis of Hepatocellular carcinoma (HCC) cells. However, it is unclear about the roles of YY1 in the sensitivity of HCC cells to HDACi. In this study, firstly, we identified two drug-response profiles to HDACi in HCC cell lines, while our results showed that HDAC1 expression was positively correlated with YY1 in HCC cell lines and primary tumor tissues. Secondly, YY1 decreased the sensitivity of HCC cells to HDACi in vitro and in vivo. Furthermore, we found that YY1 promoted HDAC1 expression by binding to its promoter, while HDAC1 in turn up-regulated the expression of YY1. In conclusion, our results showed that YY1 could reduce the sensitivity of HCC cells to HDACi and might be a potential therapeutic target in HCC.

Background: MiR-1323 was identified in 2006. Until now, the roles and mechanisms of miR-1323 in the progression of cancers including hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to investigate the expressions, roles and mechanisms of miR-1323 in HCC development. Methods: QRT-PCR was used to evaluate the expressions of miR-1323, GAS5 and TP53INP1 in HCC tissues and cell lines. CCK-8 assay, transwell invasion assay and flow cytometry assay were conducted to evaluate the proliferation, invasion and apoptosis of HCC cells. Luciferase assay was used to identify microRNA-target interaction. Results: Firstly, our results showed that miR-1323 promoted proliferation and invasion, and inhibited apoptosis of HCC cells. Secondly, we found that TP53INP1 was a direct target of miR-1323 and could reverse the effects of miR-1323 on proliferation, invasion and apoptosis of HCC cells. Thirdly, our results showed that long non-coding RNA (lncRNA) GAS5 and miR-1323 could interact with each other and affect biological processes of HCC cells. Furthermore, we identified the negative correlations between miR-1323 and TP53INP1, and between miR-1323 and GAS5 in tumor tissues of patients with HCC. Conclusion: Taken together, our study revealed the important roles of GAS5/miR-1323/TP53INP1 axis in HCC progression. This study also provided promising strategies for targeted therapy of patients with HCC.

Graphical abstract, Highlights • Expressions of ACE2 and TMPRSS2 were observed in the extrapulmonary organs. • Direct infections of SARS-CoV-2 in extrapulmonary organs were observed in patients with COVID-19. • Clinical manifestation and management for extrapulmonary organ injuries in COVID-19 should be noticed. • There might be a relationship between the infection of extrapulmonary organs and positive SARS-CoV-2 test in recovered patients., At the end of 2019, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Currently, it is breaking out globally and posing a serious threat to public health. The typically clinical characteristics of COVID-19 patients were fever and respiratory symptoms, and a proportion of patients were accompanied by extrapulmonary symptoms including cardiac injury, kidney injury, liver injury, digestive tract injury, and neurological symptoms. Angiotensin converting enzyme 2 (ACE2) has been proven to be a major receptor for SARS-CoV-2 and could mediate virus entry into cells. And transmembrane protease serine 2 (TMPRSS2) could cleave the spike (S) protein of SARS-CoV-2, which facilitates the fusion of SARS-CoV-2 and cellular membranes. The mRNA expressions of both ACE2 and TMPRSS2 were observed in the heart, digestive tract, liver, kidney, brain and other organs. SARS-CoV-2 may have a capacity to infect extrapulmonary organs due to the expressions of ACE2 and TMPRSS2 in the cells and tissues of these organs. It seems that there is a potential involvement of ACE2 and TMPRSS2 expressions in the virus infection of extrapulmonary organs and the manifestation of symptoms related to these organs in patients with COVID-19. Here, we revealed the expressions of ACE2 and TMPRSS2 in extrapulmonary organs, and we also summarized the clinical manifestation and the management of extrapulmonary complications in patients with COVID-19.

Since the molecule of Ca2+-activated Cl- channels (CaCC) had been identified as ANO1, major progresses have been made in recent studies on its roles in vascular functions. ANO1 has been confirmed to represent the CaCC channels in vascular smooth myocytes (VSMCs). Generally, ANO1 expresses more in resistance-size small arteries. When activated, it functions to control the VSMC membrane potentials by depolarization. As a result, the voltage-dependent Ca2+ channel is opened, leading to Ca2+ entry and VSMC contraction. Thus, the function of ANO1 is important for maintenance of normal blood pressure. Under influence of agonists, e.g., angiotensin II, ANO1 also participates in VSMC differentiation and remodeling which are mediated by KLF5, myocardin and SRF. The factors regulate the transcription of the ANO1 gene and other genes for VSMC differentiation and proliferation.

MicroRNAs (miRNAs) have been reported to play important roles in tumor progression of various cancers. However, the clinical significance and biologic function of miR-766 in hepatocellular carcinoma (HCC) remain unknown. In this study, we investigated the roles of miR-766 in HCC progression using HCC cell lines and a xenograft mouse model. miR-766 expression in tumor tissues and adjacent nontumorous liver tissues of patients with HCC was evaluated by quantitative RT-PCR. Our results showed that miR-766 promoted proliferation and metastasis of HCC cells in vitro and in vivo and that NR3C2 was a direct target of miR-766 and involved in miR-766-mediated proliferation and metastasis of HCC cells. We also found that miR-766 affected the β-catenin signaling pathway by targeting NR3C2. Furthermore, miR-766 was significantly up-regulated in HCC tissues and was correlated with the prognosis of patients with liver cancer. Taken together, our results show that miR-766 affects HCC progression by modulating NR3C2 expression and is a possible new therapeutic target for patients with HCC.-Yang, C., Ma, X., Guan, G., Liu, H., Yang, Y., Niu, Q., Wu, Z., Jiang, Y., Bian, C., Zang, Y., Zhuang, L. MicroRNA-766 promotes cancer progression by targeting NR3C2 in hepatocellular carcinoma.

Background Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is considered to be an oncogene in many cancer types. However, the role of DANCR in diagnosis and progression of hepatocellular carcinoma (HCC) is still unknown. Patients and methods In this study, 146 participants including healthy volunteers (HVs) and patients with chronic hepatitis B (CHB), cirrhosis and HCC were recruited. Results Firstly, quantitative reverse transcription-PCR analysis showed that DANCR was up-regulated in tumor tissues and plasma of patients with HCC, and its expression was highly correlated with microvascular and liver capsule invasion of HCC. Receiver operating characteristic analysis showed that plasma DANCR exhibited significantly increased discriminatory power for differentiating patients with HCC from HVs and non-HCC patients compared to alpha fetoprotein, which has been used as a biomarker for HCC diagnosis. Furthermore, knockdown of DANCR repressed the β-catenin pathway and inhibited HCC cell proliferation and metastasis both in vitro and in vivo. Conclusion This study revealed, for the first time, the importance of DANCR in clinical diagnosis and disease progression of HCC.

To investigate the mechanisms by which retinoic acid-induced gene G (RIG-G) protein regulates p21 gene expression.Western blot was used to detect the effects of RIG-G protein overexpression on p21 protein expression level in leukemia cell line NB4 cells and the phosphorylation of both c-Jun and JNK in U937 cells. The c-Jun expression plasmid and p21 gene promoter-containing reporter plasmid were co-transfected into 293T cells, to explore the regulatory effect of c-Jun protein on p21 gene expression by luciferase reporter assay.Western blot showed that the overexpression of RIG-G protein significantly upregulated p21 protein level in the NB4 cells, and the level of p21 protein largely increased along with the induction of endogenous RIG-G protein during the differentiation of NB4 cells treated by all-trans retinoic acid (ATRA). Moreover, the phosphorylation of both c-Jun and JNK decreased in RIG-G-overexpressing U937 cells while total c-Jun and JNK proteins remained unchanged. After using the JNK inhibitor SP600125 to block JNK phosphorylation, the level of c-Jun phosphorylation was still dramatically reduced in the RIG-G-overexpressing U937T-RIG-G cells, compared with the control U937T-pTRE cells. These results indicated that the inhibitory effect of Rig-G protein on c-Jun phosphorylation could not only be through the JNK pathway, but also via some JNK-independent pathways. Luciferase reporter assay showed that when 0.1, 0.5, 1.0 and 2.0 µg c-Jun-expressing plasmids were respectively transfected into 293T cells, compared with the empty vector-transfected group, the relative luciferase activities were (83.0 ± 1.7)%, (73.7 ± 0.7)%, (68.9 ± 0.9)% and (64.1 ± 0.9)%, indicating that the transcriptional activity of p21 gene could be inhibited by c-Jun protein.RIG-G protein may suppress the phosphorylation of c-Jun protein through different signal pathways, thereby increasing the expression of p21 gene, arresting the cell cycle and inhibiting the cell growth in U937 cells.

Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life worldwide, whereas the etiology and pathogenesis of HCC have not been fully determined. In the past few years, many microRNAs (miRNAs) have been proved to have important roles in tumorigenesis of HCC. In this study, we found that miR-23b was significantly upregulated in tumor tissues of HCC patients. Functional tests showed that miR-23b could promote HCC cell proliferation and metastasis in vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a direct target of miR-23b and involved in the promotion effects of miR-23b on HCC tumorigenesis and metastasis. Furthermore, our study indicated that ST7L could interact with the carboxyl terminal region of AKT and suppress AKT/GSK3β/β-catenin pathway in HCC cells. In conclusion, our study revealed important roles of miR-23b and ST7L in progression of HCC.

MicroRNA (miRNA) and long non-coding RNA (lncRNA) have been demonstrated to participate in the progression of many cancers. Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors worldwide, while the molecular mechanisms underlying HCC tumorigenesis are not completely clear. In this study, we showed that miR-92b was significantly upregulated in tumor tissue and plasma of HCC patients, and its expression level was highly correlated with gender and microvascular invasion. Functionally, miR-92b could promote cell proliferation and metastasis of HCC in vitro and in vivo. Mechanistic investigations suggested that Smad7, which exhibited an inverse relationship with miR-92b expression in HCC, was a direct target of miR-92b and could reverse its effects on HCC tumorigenesis. Furthermore, long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and miR-92b could directly interact with and repress each other, and XIST could inhibit HCC cell proliferation and metastasis by targeting miR-92b. Taken together, our study not only revealed for the first time the importance of XIST/miR-92b/Smad7 signaling axis in HCC progression but also suggested the potential value of miR-92b as a biomarker in the clinical diagnosis and treatment of HCC.