Abstract
Pancreatic adenocarcinoma (PDAC) is a highly fatal disease worldwide. MicroRNAs (miRNAs) could regulate the protein-coding RNAs related to tumor growth, invasion, and immune evasion. Therefore, the investigation of novel miRNAs may be helpful in the development of more effective therapies for PDAC. In this study, we investigated the role and mechanism of action of miR-128 in PDAC. By using bioinformatics methods, we found that decreased expression of miR-128 was associated with poor overall survival of PDAC. miR-128 was inversely correlated with cluster of differentiation 47 (CD47), which was positively related to zinc finger E-box-binding homeobox 1 (ZEB1) in PDAC. Through in vivo experiments, we found that miR-128 could suppress the growth and metastasis of PDAC. Analysis of the immune microenvironment demonstrated that overexpression of miR-128 on tumor cells could increase the percentages of dendritic cells (DCs), CD8+ T lymphocytes, and natural killer T cells (NKT) in the tumor and spleen, consequently enhancing anti-tumor immunity. In vitro assays showed that miR-128 could inhibit cell proliferation, clonogenicity, migration, and invasion in Panc02 cells and could also enhance the phagocytosis of macrophages and the activity of DCs. Western blot and qRT-PCR confirmed that miR-128 could regulate ZEB1 and further inhibit CD47 in pancreatic cancer cells. Therefore, we identified a novel regulatory anti-tumor mechanism by miR-128 in PDAC, which may serve as a novel therapy for PDAC.
Highlights
Pancreatic adenocarcinoma (PDAC) is one of the most aggressive and lethal solid tumors and is currently the fourth most common cause of cancer-related mortality in the developed world (1)
This suggests that miR-128 is closely related to the expression of cluster of differentiation 47 (CD47) and zinc finger E-box-binding homeobox 1 (ZEB1) in clinical patients who suffer from PDAC
Numerous studies have shown that microRNAs are clinically related to tumor proliferation, invasion, metastasis, and miR-128 Enhances Anti-tumor Immunity chemo-resistance in patients suffering from PDAC (29–31)
Summary
Pancreatic adenocarcinoma (PDAC) is one of the most aggressive and lethal solid tumors and is currently the fourth most common cause of cancer-related mortality in the developed world (1). Cluster of differentiation 47 (CD47) ( known as integrinassociated protein) is a cell surface transmembrane protein of the immunoglobulin superfamily that plays important roles in self-recognition (5). Epithelial–mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features and is associated with tumor initiation, malignant progression, tumor cell migration, invasion and metastatic spread, tumor stemness, and resistance to therapy (13). It is orchestrated by a series of master EMT-inducing transcription factors (EMT-TFs) and often defined by the loss of the epithelial marker E-cadherin and the gain of the mesenchymal marker Vimentin (14). The zinc finger E-box-binding homeobox 1 (ZEB1) is a crucial EMT activator in several cancers (15, 16), closely related to tumor initiation and malignant progression (13, 17), which can regulate CD47 (18)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
