Lin28B facilitates the progression and metastasis of pancreatic ductal adenocarcinoma

摘要

Lin28B, a Lin28 homologue, represses the biogenesis of let-7 microRNAs (miRNAs), has a role in tumorigenesis, and is considered a potential therapeutic target for various human malignancies. However, the associations between Lin28B and the clinical features and outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we explored the clinical significance of Lin28B in PDAC and its association with metastasis by examining tissues from patients with PDAC and elucidated the molecular mechanisms using PDAC cell lines. In patients, high Lin28B expression was significantly correlated with high levels of lymphatic metastasis, distant metastasis and a poor prognosis. Furthermore, the multivariate analysis identified Lin28B expression as an independent prognostic factor in patients. In cell lines, stable silencing of Lin28B inhibited cell proliferation, cell cycle transition, migration and the epithelial-mesenchymal transition (EMT). It also increased the expression of the c-MYC, HMGA2 and KRAS genes, which are targeted by the cancer-suppressor miRNA let-7. Lin28B overexpression in the PDAC cell lines had the opposite effect. In human PDAC samples, high Lin28B expression was associated with decreased let-7 expression and increased c-MYC, HMGA2 and KRAS expression. Thus, Lin28B is a novel marker for predicting the prognosis of patients with PDAC and might be a potential therapeutic target for PDAC.