GPRC5B在胰管腺癌中參與上皮-間葉的轉型過程

Abstract

Pancreatic cancer is a lethal disease needing vigorous bio-medical research. We have established a pancreatic cancer cell line, KM cells, from a patient with poorly-differentiated ductal adenocarcinoma (PDAC). In order to dig out novel genetic alterations and potential treatment targets, genome-wide studies have been carried out. In the transcriptome study, the fusion of DCUN1D3 5’-UTR and GPRC5B coding region yields the highest read numbers that support the fusion event. The fusion is verified by PCR followed by Sanger sequencing at both transcript and genome levels. We demonstrate that small interfering/hairpin RNA knockdown of GPRC5B in KM cells changes cell morphology from mesenchymal-like to epithelia-like. Moreover, migration and invasion abilities are attenuated when GPRC5B expression is downregulated. These findings are supported by the RT-qPCR and Western Blot results in that the expression of epithelial-mesenchymal transition (EMT)-related markers, such as SNAI1, SLUG, Vimentin and N-cadherin, are suppressed while the expression of E-cadherin is increased at both transcript and protein levels when GPRC5B is knocked down. The results demonstrated in this study suggest that GPRC5B may play a certain role in PDAC EMT and thus metastases. The role of DCUN1D3 5’-UTR in the regulation of GPRC5B gene expression needs further investigation. This is the first study of GPRC5B in oncology field. Detailed mechanism and involved signaling pathways deserve further studies to clarify its molecular functions in cancer.