Abstract:
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.
