Downregulation of the adenosine a2b receptor by RNA interference inhibits hepatocellular carcinoma cell growth.
Ontology highlight
ABSTRACT:
SUBMITTER: Xiang HJ
PROVIDER: S-EPMC3195956 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The adenosine A2b receptor (A2bR) was considered to play an oncogenic role in many human malignancies. However, the expression and molecular function of A2bR in bladder urothelial carcinoma (BUC) have not been well elucidated. Herein, we found that the expression of A2bR was higher than other adenosine receptors in BUC tissues and cells, and it was upregulated in BUC tissues compared with matched normal bladder tissues. Furthermore, high expression of A2bR was associated with poor prognosis of patients with BUC. In addition, suppression of A2bR inhibited the proliferation, migration and invasion of BUC cells and arrested the cell cycle at the G1 phase. Finally, we demonstrated that downregulation of A2bR inhibited the proliferation, migration and invasion of BUC in part via the MAPK signaling pathway, increasing the levels of P21 but decreasing the levels of cyclin B1, D, E1, MMP-2 and MMP-9. Overexpression of MMP-2 could rescue BUC cells migration and invasion. Thus, the present study indicates that A2bR may play a potential oncogenic role in BUC progression and act as a potential biomarker to identify BUC patients with poor clinical outcomes.
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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive potential of ESCC cells in vitro and in vivo in immunodeficient mice.MethodsWe utilized RNA interference to knockdown Slug gene expression, and effects on survival and invasive carcinoma were evaluated using a Boyden chamber transwell assay in vitro. We evaluated the effect of Slug siRNA-transfection and Slug cDNA-transfection on E-cadherin and Bcl-2 expression in ESCC cells. A pseudometastatic model of ESCC in immunodeficient mice was used to assess the effects of Slug siRNA transfection on tumor metastasis development.ResultsThe EC109 cell line was transfected with Slug-siRNA to knockdown Slug expression. The TE13 cell line was transfected with Slug-cDNA to increase Slug expression. EC109 and TE13 cell lines were tested for the expression of apoptosis-related genes bcl-2 and metastasis-related gene E-cadherin identified previously as Slug targets. Bcl-2 expression was increased and E-cadherin was decreased in Slug siRNA-transfected EC109 cells. Bcl-2 expression was increased and E-cadherin was decreased in Slug cDNA-transfected TE13 cells. Invasion of Slug siRNA-transfected EC109 cells was reduced and apoptosis was increased whereas invasion was greater in Slug cDNA-transfected cells. Animals injected with Slug siRNA-transfected EC109 cells exhibited fewer seeded nodes and demonstrated more apoptosis.ConclusionsSlug down-regulation promotes cell apoptosis and decreases invasion capability in vitro and in vivo. Slug inhibition may represent a novel strategy for treatment of metastatic ESCC.
| S-EPMC3118191 | biostudies-literature