RIP-SEQ analysis of CGN binding mRNA in PANC-1 cells stably expressing CGN
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies for its difficult early diagnosis and poor prognosis. The molecular determinants dictating pancreatic cancer initiation and progression remain to be defined and are essential to its effective early detection and successful treatment. Little is known on the cingulin (CGN) expression and function in carcinogenesis. In this study, we demonstrate the critical oncogenic role of CGN in PDAC pathogenesis. Increased expression of CGN promoted pancreatic acinar-to-ductal metaplasia (ADM) and CGN is progressively upregulated during pancreatic cancer initiation and progression. CGN was required for pancreatic cancer cell proliferation, gemcitabine resistance, tumorigenesis and invasion and its overexpression predicted a poor patient prognosis. Mechanistically, CGN enhanced EGFR/AXL/ERK signaling pathway through increasing the mRNA stabilization and the protein expression of nuclear-cytoplasmic transport protein, importin-7 (IPO7) and the nuclear translocation of pERK, thus promoting the malignant behaviors of PDAC cells. Therefore, our study has demonstrated that CGN forms a novel oncogenic signaling axis, which could be an effective therapeutic target for PDAC treatment. Overall design: To investigate the function of CGN in PDAC progression, we established PANC-1-CGN cell lines with CGN overexpressed. Then we analysis of CGN binding mRNA in human PANC-1-CGN cell lines from RIP-SEQ (input, IP)