1.The mechanism of HBV disruption on RIG-I signaling pathway.
Libo YAN ; Feijun HUANG ; Hong TANG
Journal of Biomedical Engineering 2012;29(5):995-1013
Hepatitis B virus (HBV) infection disrupt the innate immunity response, which may play an important role in the chronic mechanism, while retinoic acid-induced gene I (RIG-I) mediated signaling pathway is one of the most important channel in the innate immunity. HBx and HBV polymerase may disrupt RIG-I mediated signaling pathway. The recent advances about HBV and RIG-I are reviewed in this article.
DEAD Box Protein 58
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DEAD-box RNA Helicases
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metabolism
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Gene Products, pol
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metabolism
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Hepatitis B
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immunology
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Humans
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Immunity, Innate
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immunology
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Signal Transduction
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Trans-Activators
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metabolism
2.Retinoic acid inducible gene-I, more than a virus sensor.
Protein & Cell 2011;2(5):351-357
Retinoic acid inducible gene-I (RIG-I) is a caspase recruitment domain (CARD) containing protein that acts as an intracellular RNA receptor and senses virus infection. After binding to double stranded RNA (dsRNA) or 5'-triphosphate single stranded RNA (ssRNA), RIG-I transforms into an open conformation, translocates onto mitochondria, and interacts with the downstream adaptor mitochondrial antiviral signaling (MAVS) to induce the production of type I interferon and inflammatory factors via IRF3/7 and NF-κB pathways, respectively. Recently, accumulating evidence suggests that RIG-I could function in non-viral systems and participate in a series of biological events, such as inflammation and inflammation related diseases, cell proliferation, apoptosis and even senescence. Here we review recent advances in antiviral study of RIG-I as well as the functions of RIG-I in other fields.
Antiviral Agents
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chemistry
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DEAD Box Protein 58
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DEAD-box RNA Helicases
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chemistry
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metabolism
;
physiology
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Humans
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Inflammation
;
metabolism
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Interferon Regulatory Factor-3
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metabolism
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NF-kappa B
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metabolism
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RNA Viruses
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metabolism
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RNA, Double-Stranded
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metabolism
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Signal Transduction
3.DEXH-Box protein DHX30 is required for optimal function of the zinc-finger antiviral protein.
Peiying YE ; Shufeng LIU ; Yiping ZHU ; Guifang CHEN ; Guangxia GAO
Protein & Cell 2010;1(10):956-964
The zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by eliminating viral mRNAs in the cytoplasm. In previous studies, we demonstrated that ZAP directly binds to the viral mRNAs and recruits the RNA exosome to degrade the target RNA. In this article, we provide evidence that a DEXH box RNA helicase, DHX30, is required for optimal antiviral activity of ZAP. Pull-down and co-immunoprecipitation assays demonstrated that DHX30 and ZAP interacted with each other via their N terminal domains. Downregulation of DHX30 with shRNAs reduced ZAP's antiviral activity. These data implicate that DHX30 is a cellular factor involved in the antiviral function of ZAP.
Cytoplasm
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metabolism
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physiology
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DEAD-box RNA Helicases
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metabolism
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Humans
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Immunoprecipitation
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Protein Binding
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physiology
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RNA
;
metabolism
;
physiology
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RNA Helicases
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metabolism
;
physiology
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RNA, Messenger
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metabolism
;
physiology
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RNA, Viral
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metabolism
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RNA-Binding Proteins
;
metabolism
4.Expression of helicase DDX41 in human dental pulp tissues and cells.
Xiao-Jun YANG ; Jin HOU ; Xin-Zhu LI ; Jiao HU
Journal of Southern Medical University 2015;35(4):587-590
OBJECTIVETo detect the expression of D-E-A-D-box polypeptide 41 (DDX41) in human dental pulp tissues and cells.
METHODSThe mRNA and protein expressions of DDX41 in human dental pulp cells were detected by RT-PCR and immunocytochemistry, and the expression of DDX41 in human dental pulp tissues was investigated by immunohistochemistry.
RESULTSStrong expressions of DDX41 mRNA and protein were detected in dental pulp cells. In dental pulp tissues, DDX41 was expressed in the cytoplasm and nucleus of odontoblasts.
CONCLUSIONDDX41/STING-dependent TBK1-IRF3-IFN-β signaling pathway may play a role in innate immune responses of the dental pulp to caries and pulpitis.
Cell Nucleus ; metabolism ; Cells, Cultured ; Cytoplasm ; metabolism ; DEAD-box RNA Helicases ; metabolism ; Dental Pulp ; metabolism ; Humans ; Immunohistochemistry ; Odontoblasts ; metabolism ; RNA, Messenger ; Signal Transduction
5.Investigation of androgen receptor-dependent alternative splicing has identified a unique subtype of lethal prostate cancer.
Sean SELTZER ; Paresa N GIANNOPOULOS ; Tarek A BISMAR ; Mark TRIFIRO ; Miltiadis PALIOURAS
Asian Journal of Andrology 2023;25(3):296-308
A complete proteomics study characterizing active androgen receptor (AR) complexes in prostate cancer (PCa) cells identified a diversity of protein interactors with tumorigenic annotations, including known RNA splicing factors. Thus, we chose to further investigate the functional role of AR-mediated alternative RNA splicing in PCa disease progression. We selected two AR-interacting RNA splicing factors, Src associated in mitosis of 68 kDa (SAM68) and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) to examine their associative roles in AR-dependent alternative RNA splicing. To assess the true physiological role of AR in alternative RNA splicing, we assessed splicing profiles of LNCaP PCa cells using exon microarrays and correlated the results to PCa clinical datasets. As a result, we were able to highlight alternative splicing events of clinical significance. Initial use of exon-mini gene cassettes illustrated hormone-dependent AR-mediated exon-inclusion splicing events with SAM68 or exon-exclusion splicing events with DDX5 overexpression. The physiological significance in PCa was investigated through the application of clinical exon array analysis, where we identified exon-gene sets that were able to delineate aggressive disease progression profiles and predict patient disease-free outcomes independently of pathological clinical criteria. Using a clinical dataset with patients categorized as prostate cancer-specific death (PCSD), these exon gene sets further identified a select group of patients with extremely poor disease-free outcomes. Overall, these results strongly suggest a nonclassical role of AR in mediating robust alternative RNA splicing in PCa. Moreover, AR-mediated alternative spicing contributes to aggressive PCa progression, where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.
Humans
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Male
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Alternative Splicing
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Cell Line, Tumor
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DEAD-box RNA Helicases/metabolism*
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Disease Progression
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Gene Expression Regulation, Neoplastic
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Prostatic Neoplasms/pathology*
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Receptors, Androgen/metabolism*
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RNA Splicing Factors/metabolism*
6.The Latest Research Progress on Myelodysplastic Syndrome Patient-derived Mesenchymal Stem Cell--Review.
Fan LI ; Hai-Ping HE ; Li-Hua ZHANG ; Xiao-Sui LING
Journal of Experimental Hematology 2022;30(4):1286-1290
Myelodysplastic syndrome (MDS) are a heterogeneous group of hematological malignancies. Currently, in addition to demethylated chemotherapy and hematopoietic stem cell transplantation, MDS patient-derived mesenchymal stem cells (MDS-MSC) play an important role in understanding the pathogenesis of MDS and related therapeutic targets. For example, abnormal expression of DICER1 gene, abnormalities of PI3K/AKT and Wnt/β-catenin signaling pathways provide new therapeutic targets for MDS. In addition, MDS-MSC is also affected by abnormal microenvironment of the body, such as inflammatory factor S100A9, as well as hypercoagulation and iron overload. In this review, genes, signaling pathways, cytokines, hematopoietic microenvironment, and the effect of therapeutic drugs for MDS-MSC were briefly summarized.
Cytokines/metabolism*
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DEAD-box RNA Helicases/metabolism*
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Hematologic Neoplasms/metabolism*
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Humans
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Mesenchymal Stem Cells
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Myelodysplastic Syndromes/genetics*
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Phosphatidylinositol 3-Kinases/metabolism*
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Ribonuclease III/metabolism*
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Tumor Microenvironment
7.Relationship between the expression of DDX39 protein and prognosis of colorectal cancer.
Jun MA ; Wenjun CHANG ; Wei ZHANG
Chinese Journal of Gastrointestinal Surgery 2018;21(3):336-341
OBJECTIVETo investigate the relationship between the expression of DDX39 protein and prognosis in colorectal cancer.
METHODSClinical data and paraffin specimens of postoperative tumor tissue from 824 patients with primary colorectal cancer who received first surgical treatment at the Department of Colorectal Surgery of Changhai Hospital of Navy Military Medical University from January 2010 to December 2011 were collected. Paraffin samples of paracancerous tissues of 38 patients were served as controls. At the same time, samples of normal rectal mucous membrane from 37 cases after procedure of prolapse and hemorrhoids, and samples of colorectal adenoma from 33 cases after endoscopic treatment were enrolled in this study. All the specimens were made as the tissue microarray, and the expression of DDX39 protein was detected by immunohistochemistry. The expression of DDX39 in the epithelium and stroma was evaluated with the average staining intensity (H-Score) and the number of positive cells. It was defined as high expression in the epithelium that the H-Score was greater than or equal to 200. It was defined as high expression in the stroma that the number of positive cells was greater than or equal to 50 in 200 times the field of vision. Relationship of different DDX39 expression levels with clinicopathological parameters and prognosis of colorectal cancer was analyzed.
RESULTSThe expression of DDX39 in colorectal cancer tissues was lower than that in normal tissues, paracancerous tissues and adenomatous tissues, whether it is in the epithelium or in the stroma [DDX39 expression in the epithelium: normal tissues 253.2±64.1, paracancerous tissues 238.8±79.2, adenomatous tissues 259.4±51.6, colorectal cancer tissues 194.2±76.5 (P=0.000, P=0.005, P=0.000, respectively); DDX39 expression in the stroma: normal tissues 110.1±64.8, paracancerous tissues 106.0±49.2, adenomatous tissues 108.5±79.1, colorectal cancer tissues 54.1±34.7(all P=0.000)]. Among the cases of colorectal cancer, there were 541 cases of high DDX39 expression and 283 cases of low DDX39 expression in the epithelium; there were 424 cases of high DDX39 expression of and 400 cases of low DDX39 expression in the stroma. The high DDX39 expression and low DDX39 expression in epithelial and stromal of colorectal cancer were related respectively with tumor location (P=0.006, P=0.016), degree of tumor differentiation (P=0.002, P=0.064), TNM stage (P=0.021, P=0.000), serum CEA level (P=0.003, P=0.005), serum CA199 level (P=0.040, P=0.005) and tumor recurrence and metastasis (P=0.000, P=0.000). All the colorectal cancer cases were followed up for (41.6±15.7) months after operation. The 5-year overall survival (OS) and disease-free survival (DFS) rates of the cases with epithelial low DDX39 expression were 84.1% and 61.5%, and both were significantly lower as compared to those with epithelial high DDX39 expression (95.4% and 88.2%, P=0.000, P=0.000). The 5-year OS and DFS rates of the stroma low DDX39 expression were 86.8% and 66.8%, and both were significantly lower as compared to those with stroma high DDX39 expression (96.1% and 90.6%, P=0.000, P=0.000). Cox multivariate analysis showed that tumor differentiation (OS:HR=0.252, 95%CI: 0.128 to 0.497, P=0.000; DFS:HR=0.266, 95%CI: 0.134 to 0.530, P=0.000), DDX39 expression level in epithelium (OS: HR =0.229, 95%CI: 0.138 to 0.382, P=0.000; DFS: HR =0.266, 95%CI: 0.158 to 0.446, P=0.000), and DDX39 expression level in stroma (OS: HR =0.331, 95%CI: 0.188 to 0.582, P=0.000; DFS:HR=0.326, 95%CI: 0.184 to 0.578, P=0.000) were independent influencing factors of overall or disease-free survival in patients with colorectal cancer.
CONCLUSIONThe low expression of DDX39 protein suggests poor prognosis and DDX39 is expected to be a new prognostic marker of colorectal cancer.
Biomarkers, Tumor ; metabolism ; Colonic Neoplasms ; Colorectal Neoplasms ; metabolism ; pathology ; DEAD-box RNA Helicases ; metabolism ; Disease-Free Survival ; Humans ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis
8.Reduced expression of Diceri is associated with poor prognosis in patients with nasopharyngeal carcinoma.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2015;29(2):126-131
OBJECTIVE:
Dicerl plays an important role in generation of microRNA, the purpose of this study was to evaluate Dicerl expression and its prognostic value in nasopharyngeal carcinoma (NPC).
METHOD:
The protein expression of Dicerl was examined by immunohistochemistry in 276 NPC specimens, and the mRNA levels of Dicerl were analyzed by qRT-PCR in 56 NPC and 11 nasopharyngitis tissues. Cox regression analysis was used to identify independent prognostic factors, and a prognostic score model was constructed for survival prediction.
RESULT:
Expression of Dicerl was downregulated in NPC tissues at both the mRNA and the protein levels, and there was a notable positive correlation between the expression levels of Dicerl mRNA and protein. Low Dicerl expression was positively correlated with distant metastasis (P<0. 01) and death (P<0. 05). In addition, low expression of Dicerl was significantly associated with poorer overall survival (HR = 2. 32, 95% CI: 1. 30 ~ 4. 14, P<0. 01) and poorer distant metastasis-free survival (HR = 2. 56, 95% CI: 1. 39 ~ 4. 74, P<0. 01). Furthermore, multivariate analysis showed that low expression of Dicerl and tumor-node-metastasis (TNM) stage were independent prognostic indicators for NPC patients. A prognostic score model combining the Dicerl expression and TNM stage had a better prognostic value than the TNM stage alone model or Dicer) expression alone model (P< 0. 05).
CONCLUSION
Dicerl was downregulated in NPC tissues at both the mRNA and the protein levels, and low expression of Dicerl could be served as novel prognostic biomarker for NPC patients.
Carcinoma
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DEAD-box RNA Helicases
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biosynthesis
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Humans
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Immunohistochemistry
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Nasopharyngeal Carcinoma
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Nasopharyngeal Neoplasms
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metabolism
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pathology
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Prognosis
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Proteomics
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RNA, Messenger
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Ribonuclease III
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biosynthesis
9.Spermatozoal protein profiles in male infertility with asthenozoospermia.
Hong-jun LI ; Ning YU ; Xin-yu ZHANG ; Wei JIN ; Han-zhong LI
Chinese Medical Journal 2010;123(20):2879-2882
BACKGROUNDInfertility is a major medical and social problem, and elementary research on the spermatozoal proteins and their functions are relatively scarce and there are very few confirmed and effective options for the treatment of male infertility. Thus, it is essential to find candidate proteins that affect male infertility. This study was designed to detect the proteins with differential expression in sperm from infertile patients and normal donors.
METHODSSemen samples from patients with idiopathic asthenozoospermia (n = 114) and from fertile men with normal spermiograms (n = 37) were collected. Semen sample analysis, sperm protein extraction, SDS-PAGE electrophoresis and Western blotting analysis were performed. Results were analyzed by SPSS 16.0 statistical software.
RESULTSWestern blotting analysis of spermatic proteins displayed a major differentially expressed protein in spermatozoa from fertile and idiopathic asthenozoospermia patients. Densities and volumes of the identified protein in the patients were significantly decreased compared to normal donors (P = 0.034 and P = 0.036, respectively). The protein was identified as DEAD-box protein 4 (DDX4, VASA). The expression and correction value (CV) of DDX4/VASA in the patients was reduced significantly compared to normal donors (P = 0.037 and P = 0.031, respectively).
CONCLUSIONSThe expression of spermatic protein DDX4/VASA associates with spermatic motility, implying that DDX4/VASA may be a candidate marker for evaluation of spermatic motility.
Asthenozoospermia ; metabolism ; Blotting, Western ; DEAD-box RNA Helicases ; analysis ; Electrophoresis, Polyacrylamide Gel ; Humans ; Infertility, Male ; metabolism ; Male ; Sperm Motility ; Spermatozoa ; chemistry
10.microRNA-18a Promotes Cell Migration and Invasion Through Inhibiting Dicer l Expression in Hepatocellular Carcinoma In Vitro.
Xiufen ZHANG ; Bo YU ; Fuzheng ZHANG ; Zijian GUO ; Lihua LI
Chinese Medical Sciences Journal 2017;32(1):34-33
Objective To investigate the effects of microRNA-18a (miR-18a) on migration and invasion of hepatocellular carcinoma (HCC) cells, and its possible mechanism associated with Dicer l.Methods HepG2 and HepG2.2.15 cells were transfected with miR-18a inhibitor using Lipofectamine. Cell invasion was evaluated by transwell invasion assay, and cell migration was detected by transwell migration and wound-healing assays. Moreover, luciferase reporter assay was used to identify whether Dicer expression was regulated by miR-18a. Real-time RT-PCR and western blot were performed to analyze Dicer 1 expression. In addition, a functional restoration assay was performed to investigate whether miR-18a promotes HCC cell migration and invasion by directly targeting Dicer 1.Results miR-18a inhibitor can suppress the migration and invasion of HCC cells. Furthermore, suppression of Dicer l expression by small interfering RNA essentially abolished the inhibition of cell migration and invasion induced by miR-18a inhibitor, restorating these activities to levels similar to the parental HCC cells. Interestingly, suppression of miR-18a in HCC cells resulted in enhanced expression of Dicer l. In addition, the results of a luciferase assay demonstrated targeted regulation of Dicer l by miR-18a.Conclusion Our findings suggest that miR-18a promotes migration and invasion of HCC cells by inhibiting Dicer l expression.
Carcinoma, Hepatocellular
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genetics
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metabolism
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pathology
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Cell Movement
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DEAD-box RNA Helicases
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genetics
;
metabolism
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Hep G2 Cells
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Humans
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Liver Neoplasms
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genetics
;
metabolism
;
pathology
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MicroRNAs
;
genetics
;
metabolism
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Neoplasm Invasiveness
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Neoplasm Proteins
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genetics
;
metabolism
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RNA, Neoplasm
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genetics
;
metabolism
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Ribonuclease III
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genetics
;
metabolism