Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis. To determine if genetic loss of SRC-2 is sufficient to accelerate MYC-mediated liver tumorigenesis, we bred Src-2-/- mice with a MYC-induced liver tumor model and observed a significant increase in liver tumor burden. RNA sequencing of liver tumors and in vivo chromatin immunoprecipitation assays revealed a set of direct target genes that are bound by SRC-2 and exhibit downregulated expression in Src-2-/- liver tumors. We demonstrate that activation of SHP (Small Heterodimer Partner), DKK4 (Dickkopf-4), and CADM4 (Cell Adhesion Molecule 4) by SRC-2 suppresses tumorigenesis in vitro and in vivo. These studies suggest that SRC-2 may exhibit oncogenic or tumor suppressor activity depending on the target genes and nuclear receptors that are expressed in distinct tissues and illuminate the mechanisms of tumor suppression by SRC-2 in liver.
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PMID:SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer. 2964 18

Aberrant expression of long non-coding RNA DSCAM-AS1 (Down Syndrome Cell Adhesion Molecule antisense) has been observed in several cancers. However, the expression status, biological function and underling mechanism of DSCAM-AS1 in hepatocellular carcinoma (HCC) remain unclear. The expression of DSCAM-AS1 was detected in HCC tissues and serum from both HCC patients and healthy controls. MTS, wound healing and transwell invasion assays were used to examine the effects of DSCAM-AS1 on cell proliferation, migration, and invasion in HCC cells, respectively. MicroRNAs (miRNAs) targeted DSCAM-AS1 was predicated by Starbase2.0 and identified using luciferase reporter and RNA immunoprecipitation assays. The xenograft mice were established to examine the effect DSCAM-AS1 on tumor growth in vivo. We found that DSCAM-AS1 was up-regulated in HCC tissues relative to adjacent non-tumor tissues. Serum levels of DSCAM-AS1 were higher in HCC patients than that in healthy controls. Increased DSCAM-AS1 was associated with poor prognosis. Knockdown of DSCAM-AS1 significantly inhibited HCC cell proliferation, migration and invasion. Moreover, miR-338-3p was confirmed as a direct target of DSCAM-AS1 in HCC cells. The miR-338-3p inhibitor could partially reverse the inhibitory effect of DSCAM-AS1 depletion in HCC cells. DSCAM-AS1 positively regulated CyclinD1 and smoothened (SMO) expression (two targets of miR-338-3p) in HCC cells. Moreover, tumor growth was tremendously retarded in nude mice received injection of SMCC-7721 cells transfected with sh-DSCAM-AS1. Taken together, the present work suggested that DSCAM-AS1 functioned as an oncogenic lncRNA that promoted HCC progression by sponging miR-338-3p.
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PMID:Long non-coding RNA DSCAM-AS1 accelerates the progression of hepatocellular carcinoma via sponging miR-338-3p. 3139 35


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