Downregulation of the let‑7 family of microRNAs may promote insulin receptor/insulin‑like growth factor signalling pathways in pancreatic ductal adenocarcinoma

dc.contributor.authorNweke, Ekene Emmanuel
dc.contributor.authorBrand, Martin
dc.date.accessioned2021-05-18T09:19:24Z
dc.date.available2021-05-18T09:19:24Z
dc.date.issued2020
dc.description.abstractPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type characterized by dysregulated cell signalling pathways and resistance to treatment. The insulin‑like growth factor (IGF) signalling pathway has been identified to have a role in tumour progression and therapy resistance. However, its regulatory roles in PDAC have remained to be fully elucidated. In the present study, dysregulated microRNAs (miRNAs) in PDAC were explored with a focus on those that may be involved in regulating the insulin/IGF signalling pathway. A total of 208 patients were recruited, comprising 112 patients with PDAC, 50 patients with chronic pancreatitis (CP) and 46 subjects as a control group (CG). miRNA‑specific quantitative PCR assays were used to measure 300 candidate miRNAs. The Student's t‑test was applied to compare miRNA regulation between cancer patients and controls with a false discovery rate correction using Bonferroni‑type comparison procedures. The DIANA‑mirPath v.3 tool and HMDD v3.0 were used to identify miRNA‑mRNA interactions within specific pathways. In patients with PDAC, 42 miRNAs were significantly upregulated and 42 were downregulated compared to the CG (P<0.01). In the PDAC vs. CP analysis, 16 significantly (P<0.01) upregulated and 16 downregulated miRNAs were identified. Of note, members of the let‑7 family of miRNAs were downregulated and were indicated to target several components of the insulin receptor (INSR)/IGF pathway, including receptors and binding proteins, for upregulation and thus, may enable the activation of the pathway. Downregulation of the let‑7 family may help promote the INSR/IGF pathway in PDAC. It may thus be an effective target for the development of INSR/ IGF pathway‑specific treatment strategies.en_ZA
dc.description.departmentSurgeryen_ZA
dc.description.librarianam2021en_ZA
dc.description.sponsorshipThe South African National Research Foundation and South African Medical Research Council.en_ZA
dc.description.urihttp://www.spandidos-publications.com/olen_ZA
dc.identifier.citationNweke, E.E. & Brand, M. 2020, 'Downregulation of the let‑7 family of microRNAs may promote insulin receptor/insulin‑like growth factor signalling pathways in pancreatic ductal adenocarcinoma', Oncology Letters, vol. 20, pp. 2613-2620.en_ZA
dc.identifier.issn1792-1074 (print)
dc.identifier.issn1792-1082 (online)
dc.identifier.other10.3892/ol.2020.11854
dc.identifier.urihttp://hdl.handle.net/2263/79939
dc.language.isoenen_ZA
dc.publisherSpandidosen_ZA
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.en_ZA
dc.subjectLet-7en_ZA
dc.subjectDysregulated pathwaysen_ZA
dc.subjectPancreatic ductal adenocarcinoma (PDAC)en_ZA
dc.subjectInsulin‑like growth factor (IGF)en_ZA
dc.subjectMicroRNA (miRNA)en_ZA
dc.titleDownregulation of the let‑7 family of microRNAs may promote insulin receptor/insulin‑like growth factor signalling pathways in pancreatic ductal adenocarcinomaen_ZA
dc.typeArticleen_ZA

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