SHh-Gli1 signaling pathway promotes cell survival by mediating baculoviral IAP repeat-containing 3 (BIRC3) gene in pancreatic cancer cells
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The abnormally activated hedgehog (Hh) signaling pathway is involved in the regulation of proliferation and apoptosis in pancreatic cancer cells, while its exact molecular mechanism is not clear. The purpose of this study was to investigate the regulatory effect of Hh signaling pathway on the transcription of BIRC3 gene and its underlying mechanism in pancreatic cancer cells, as well as the relationship between the Gli1-dependent BIRC3 transcription and cell survival. Firstly, we examined the effect of knockdown or overexpression of Hh on BIRC3 messenger RNA (mRNA) expression by real-time RT-PCR. Then, the regulatory mechanism of Gli1 to BIRC3 gene transcription was investigated by XChIP-PCR and luciferase assays. Finally, the cell survival mediated by the Gli1-dependent BIRC3 transcription was studied by MTT and annexin V-FITC/propidiumiodide (PI) assays. We found that the expression level of BIRC3 mRNA was positively correlated to SHh/Gli1 signaling activation in three pancreatic cancer cell lines. The XChIP-PCR and luciferase assays data showed that the transcription factor Gli1 bound to some enhancers within the promoter regions of BIRC3 gene and promoted gene transcription. The cell proliferation was increased significantly by SHh/Gli1 expression while the apoptotic rate was reduced under the same condition. Moreover, BIRC3 knockdown inhibited cell proliferation and survival induced by SHh overexpression. Our study reveals that Gli1 promoted transcription of BIRC3 gene via cis-acting elements and the SHh-Gli1 signaling pathway maintained cell survival partially through this Gli1-dependent BIRC3 model in pancreatic cancer cells.
KeywordPancreatic cancer SHh-Gli1 signaling pathway BIRC3 Proliferation Apoptosis
We thank all members of the Central Laboratory of the Tenth Hospital of Tongji University.
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