Open AccessDownregulation of the let‑7 family of microRNAs may promote insulin receptor/insulin‑like growth factor signalling pathways in pancreatic ductal adenocarcinoma
Author(s) -
Ekene Emmanuel Nweke,
Martin Brand
Publication year - 2020
Publication title -
oncology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.766
H-Index - 54
eISSN - 1792-1082
pISSN - 1792-1074
DOI - 10.3892/ol.2020.11854
Subject(s) - downregulation and upregulation , microrna , oncogene , biology , cancer research , pancreatic cancer , cancer , insulin receptor , signal transduction , insulin , insulin resistance , cell cycle , receptor , medicine , endocrinology , microbiology and biotechnology , gene , genetics
Pancreatic 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.