Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TRAIL (TNF-related apoptosis-inducing ligand) is a member of the tumor necrosis factor superfamily that can induce tumor selective death by up-regulating death receptor 4 (DR4) and DR5 expression. The study aimed to explore the role of RIP and c-FLIP genes in TRAIL induced liver cancer cell HepG2 and Hep3B apoptosis and related mechanism. RIP and c-FLIP silenced HepG2 and Hep3B cell model were established through siRNA. Western blot was applied to test c-FLIP, RIP, DR4, DR5, FADD, Caspase-3/8/9, ERK1/2, and DFF45 protein expression. Caspase-8 kit was used to detect Caspase-8 expression. Flow cytometry was performed to measure cell apoptosis rate. Acid phosphatase method was applied to determine cell cycle. TRAIL had no significant effect on Caspase-3/8/9, DR4, DR5, ERK1/2, and DFF45 protein expression, but up-regulated c-FLIP and RIP protein expression and reduced FADD expression level. After treated by the chemotherapy drug mitomycin and adriamycin, c-FLIP and RIP expression decreased significantly, while FADD increased. After knockout c-FLIP and RIP gene, HepG2 and Hep3B cell apoptosis rate induced by TRAIL increased obviously. Meanwhile, cell subG1 percentage increased markedly and exhibited G1 phase growth retardation. In addition, after two kinds of gene knockout, Caspase-8 was activated and produce Caspase-3 P20 and P24, leading DFF45 appeared DNA fragment P17 and P25. c-FLIP and RIP can inhibit Caspase-8 activation and prompting HepG2 and Hep3B resistant to cell apoptosis induced by TRAIL.
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PMID:Protective effect of RIP and c-FLIP in preventing liver cancer cell apoptosis induced by TRAIL. 2626 30

Endothelial progenitor cell (EPC) recruitment and angiogenesis play crucial roles in aneurysm neck endothelialization, but the mechanisms of EPC recruitment and angiogenesis are still unclear. Recent studies have shown that long noncoding RNAs (lncRNAs) can regulate the function and differentiation of cells in various ways. LncRNA TUG1 is involved in liver cancer and glioma-mediated angiogenesis. The aim of this study was to investigate the role of lncRNA TUG1 in regulating EPC migration and differentiation. Overexpression and knockdown of lncRNA TUG1 with lentivirus, scratch assays, Transwell assays and tube formation assays using EPCs isolated from rat bone marrow showed that lncRNA TUG1 overexpression promoted EPC migration, invasion and differentiation. Moreover, ELISAs showed that lncRNA TUG1 overexpression increased VEGF expression. Bioinformatics prediction, luciferase assays, Western blots and RIP assays indicated that lncRNA TUG1 functions as a ceRNA (competing endogenous RNA) for miR-6321 and that miR-6321 inhibits EPC migration and differentiation through its target, ATF2. As a potential therapeutic target, lncRNA TUG1 may play a vital role in the pathogenesis of aneurysms.
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PMID:LncRNA TUG1 functions as a ceRNA for miR-6321 to promote endothelial progenitor cell migration and differentiation. 3193 81

Long noncoding RNA OIP5-AS1 has been observed to be increased in several cancers, however, its role and biological mechanism was poorly understood in HCC. Currently, we found OIP5-AS1 expression was upregulated in HCC cells compared with normal human liver cells. Knockdown of OIP5-AS1 suppressed HCC cell proliferation, induced cells cycle arrest and cells apoptosis. In addition, HCC cell migration and invasion capacity in vitro were also inhibited by OIP5-AS1 inhibition. Bioinformatics analysis revealed OIP5-AS1 could interact with miR-363-3p, thereby repressing HCC development. We also observed miR-363-3p was significantly decreased in HCC cells and overexpression of miR-363-3p repressed HCC progression. The correlation between OIP5-AS1 and miR-363-3p was confirmed by performing RIP assay and RNA pull-down assay. Subsequently, SOX4 was predicted as a target of miR-363-3p and miR-363-3p modulated SOX4 levels negatively in vitro. Apart from these, in vivo experiments established that OIP5-AS1 can suppress HCC development through regulating miR-363-3p and SOX4. Collectively, these demonstrated that OIP5-AS1 was involved in HCC progression via targeting miR-363-3p and SOX4. OIP5-AS1 can act as a novel candidate for HCC diagnosis, prognosis, and therapy.
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PMID:LncRNA OIP5-AS1 interacts with miR-363-3p to contribute to hepatocellular carcinoma progression through up-regulation of SOX4. 3204 27

Hepatocellular carcinoma (HCC) represents a major cause of cancer death, but the molecular mechanism for its development has not yet been well characterized. Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes via their roles as oncogenes or tumor suppressor genes. The present study aimed to elucidate the role of LINC00324 in HCC through its interaction with Fas ligand (FasL). Initially, microarray-based gene expression profiling of HCC was employed to identify differentially expressed genes. Next, the expression of LINC00324 in HCC tissues and liver cancer stem cell (LCSC) lines was examined using RT-qPCR. Then, the interaction among LINC00324, PU box binding protein (PU.1) and FasL was identified with RIP, ChIP and dual-luciferase reporter gene assays. The effect of LINC00324 on viability, proliferation, migration, invasion, and apoptosis as well as the tumorigenesis of transfected cells was examined with gain- and loss-of-function experiments. LINC00324 and FasL were highly expressed in HCC. LINC00324 regulated FasL expression via interaction with PU.1. Silencing of LINC00324 or FasL suppressed expression of stemness-related genes, cell viability, proliferation, migration, invasion, self-renewal, and tumorigenesis, but enhanced cell apoptosis. Taken together, LINC00324 promotes the expression of FasL through the recruitment of PU.1, which ultimately maintains the biological properties of LCSCs, thus, highlighting LINC00324 as a promising therapeutic candidate for HCC.
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PMID:Long noncoding RNA LINC00324 exerts protumorigenic effects on liver cancer stem cells by upregulating fas ligand via PU box binding protein. 3212 6

Hepatocellular carcinoma (HCC) is one of the important types of liver cancer. LncRNA is an important regulatory factor that regulates many biological processes such as tumor cells during tumorigenesis and metastasis. LINC00346 has been associated with various types of liver cancer, but its role and regulatory mechanism in HCC remain unclear. In our study, we found the LINC00356-miR-199a-3p-CDK1/CCNB1 axis through bioinformatics analysis. The expressions of LINC00356, miR-199a-3p, CDK1, and CCNB1 in HCC and normal hepatocytes were determined by qRT-PCR and WB. The results showed that LINC00356, CDK1 and CCNB1 were highly expressed in HCC, while miR-199a-3p was lowly expressed. Dual luciferase reporter gene assay, RIP and RNA-pull down assays demonstrated the targeted binding relationship of LINC00346-miR-199a-3p-CDK1/CCNB1. Overexpressing LINC00460 and silencing miR-199a-3p promoted cell invasion, inhibited apoptosis of HCC, and arrested the cell cycle in S phase while opposite results were obtained when silencing LINC00346, CDK1, and CCNB1. LINC00346 indirectly affects liver cancer by promoting the expression of CDK1/CCNB1 through competitive adsorption of miR-199a-3p. In addition, the study also demonstrated that overexpression of LINC00346 indirectly inhibited the expression of p53 and p21 proteins by promoting CDK1/CCNB1 expressions, thereby blocking the p53 signaling pathway. These results proved that LINC00346 could regulate the expression of CDK1/CCNB1 through the competitive adsorption of miR-199a-3p, thereby affecting the p53 signaling pathway and finally regulating the apoptosis, invasion and cell cycle of HCC cells. In conclusion, LINC00346 can be used as a tumor promoter and potential therapeutic target for HCC metastasis and prognosis.
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PMID:LINC00346 Acts as a Competing Endogenous RNA Regulating Development of Hepatocellular Carcinoma via Modulating CDK1/CCNB1 Axis. 3213 48