SHh-Gli1 signaling pathway promotes cell survival by mediating baculoviral IAP repeat-containing 3 (BIRC3) gene in pancreatic cancer cells

Abstract

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.

Identification of microRNA-124 in regulation of Hepatocellular carcinoma through BIRC3 and the NF-κB pathway

“…BIRC3, also known as cIAP2, a member of the inhibitor of apoptotic proteins (IAP) families that inhibits apoptosis by directly inhibiting caspases cascade 26 . It has been reported that BIRC3 was involved in multiple biological processes, including cell proliferation, migration and apoptosis 27 , and high expression of BIRC3 was found in variety of human malignant tumors 28 .…”

Activation of Sonic Hedgehog Signaling Is Associated with Human Osteosarcoma Cells Radioresistance Characterized by Increased Proliferation, Migration, and Invasion

“…Shh signaling is composed of Shh ligand, transmembrane receptor complex (Ptch and Smo), and the downstream nuclear transcription factor Gli. The Shh signaling pathway plays crucial roles in regulating cell differentiation, adhesion, migration, transformation, and apoptosis [ 19 ]. It was found that Shh signaling was activated in many human cancers such as gastric cancer, liver cancer, breast cancer, and ovarian cancer [ 11 , 20 ].…”

Emodin Impairs Radioresistance of Human Osteosarcoma Cells by Suppressing Sonic Hedgehog Signaling

“…Shh signaling is composed of Shh ligand, transmembrane receptor complex (Ptch and Smo), and the downstream nuclear transcription factor Gli. It was reported that Shh signaling was critical for regulating cell growth, differentiation, adhesion, and apoptosis [ 16 ]. Previous studies reported that the Shh signaling was activated in many human malignant tumors, including liver cancer, gastric cancer, and breast cancer [ 17 ].…”