EREG silencing inhibits tumorigenesis via inactivating ERK/p38 MAPK pathway in pancreatic ductal adenocarcinoma

Abstract

Epiregulin (EREG) is a member of the epidermal growth factor (EGF) family. An increasing body of evidence has demonstrated the pivotal role of EREG in the pathogenesis and progression of various malignancies. However, the clinical significance and biological role of EREG in pancreatic ductal adenocarcinoma (PDAC) have yet to be fully elucidated. We found that EREG is highly expressed in PDAC tissues compared with paracancerous tissues through public databases and clinical samples. High EREG expression predicted worse overall survival (OS) and recurrence-free survival (RFS) in patients with PDAC. Multivariate analysis revealed that EREG can serve as an independent prognostic indicator. In addition, EREG silencing inhibited PDAC cell proliferation, migration, progression, altered cell cycle, facilitated apoptosis in vitro and suppressed tumor growth in vivo. Conversely, EREG overexpression facilitated the proliferation, migration, and invasion in PaTu-8988 t cell. Through transcriptome sequencing and experimental verification, we found EREG mediates PDAC tumorigenesis through ERK/p38 MAPK signaling pathway. Moreover, we found EREG expression is closely related to PD-L1 expression in PDAC tissues and cells. Therefore, EREG is expected to be a prospective prognostic and therapeutic marker for PDAC.