Abstract
BackgroundmicroRNAs (miRNAs) play a critical role in tumorigenesis, either as a tumor suppressor or as an oncogenic miRNA, depending on different tumor types. To date, scientists have obtained a substantial amount of knowledge with regard to miRNAs in pancreatic cancer. However, the expression and function of miR-371-5p in pancreatic cancer has not been clearly elucidated. The aim of this study was to investigate the roles of miR-371-5p in pancreatic cancer and its association with the survival of patients with pancreatic cancer.MethodsThe expression of miR-371-5p was examined in pancreatic duct adenocarcinoma (PDAC) and their adjacent normal pancreatic tissues (ANPT) or in pancreatic cancer cell lines by qRT-PCR. The association of miR-371-5p expression with overall survival was determined. The proliferation and apoptosis of SW-1990 and Panc-1 cells, transfected with miR-371-5p mimics or inhibitor, were assessed using MTT assay and flow cytometry, respectively. The tumorigenicity was evaluated via mice xenograft experiments. miR-371-5p promoter interactions were analyzed by chromatin immunoprecipitation assays (ChIP). Protein expression was analyzed by Western blot.ResultsThe expression level of miR-371-5p was dramatically upregulated in clinical PDAC tissues compared with ANPT. Patients with high miR-371-5p expression had a significantly shorter survival than those with low miR-371-5p expression. The in vitro and in vivo assays showed that overexpression of miR-371-5p resulted in cell proliferation and increased tumor growth, which was associated with inhibitor of growth 1 (ING1) downregulation. Interestingly, we also found that ING1, in turn, inhibited expression of miR-371-5p in the promoter region.Conclusionsour study demonstrates a novel ING1-miR-371-5p regulatory feedback loop, which may have a critical role in PDAC. Thus miR-371-5p can prove to be a novel prognostic factor and therapeutic target for pancreatic cancer treatment.
Highlights
pancreatic duct adenocarcinoma (PDAC) is a highly malignant phenotype characterized by rapid progression, early metastasis, and a limited response to radiotherapy and chemotherapy
The MTT proliferation assay was conducted in SW-1990, and Panc-1 cells that were transiently transfected with a miR-371-5p mimic or inhibitor
The results showed that miR-371-5p -mimics promoted tumor cell growth, whereas the anti-miR-371-5p inhibited tumor cell growth (P,0.01, Fig.2C and D) To investigate the mechanism by which anti-miR-371-5 inhibits cell proliferation, we analyzed the cell cycle distribution of the Panc-1 and SW-1990 cells that were transfected with anti- miR-371-5p and the control
Summary
PDAC is a highly malignant phenotype characterized by rapid progression, early metastasis, and a limited response to radiotherapy and chemotherapy. Despite more than 10 years of FDAapproved therapeutic regimens and great improvements in medical care, no significant effect on PDAC patient survival has been observed [1]. It is the fourth leading cause of cancerrelated deaths in the U.S with a 5% 5-year survival rate annually [2]. In the past 10 years, miRNAs are important in most tumor development studies because they can be targets of genomic lesions, controlled by classic tumor signals, and they themselves present as a class of oncogenes or tumor suppressors [4]. The aim of this study was to investigate the roles of miR-371-5p in pancreatic cancer and its association with the survival of patients with pancreatic cancer
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.
