Downregulated expression of IL‑28RA is involved in the pathogenesis of pancreatic ductal adenocarcinoma

Liu,Li; Qi,Yinliang; Huang,Dake; Xu,Yechuan; Li,Mingcong; Hong,Zhou; Gu,Yanan; Jia,Bo; Luo,Xin; Zhang,Sumei; Zhang,Shengquan

doi:10.3892/ijo.2021.5235

Downregulated expression of IL‑28RA is involved in the pathogenesis of pancreatic ductal adenocarcinoma

Authors:
- Li Liu
- Yinliang Qi
- Dake Huang
- Yechuan Xu
- Mingcong Li
- Zhou Hong
- Yanan Gu
- Bo Jia
- Xin Luo
- Sumei Zhang
- Shengquan Zhang
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Affiliations: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China, General Department of Hyperbaric Oxygen, Affiliated Hefei Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China, Comprehensive Laboratory in School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Xiangyang Institute for Food and Drug Control, Xiangyang, Hubei 441000, P.R. China
Published online on: June 22, 2021 https://doi.org/10.3892/ijo.2021.5235
Article Number: 55

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Abstract

Pancreatic cancer ranks seventh in terms of cancer‑related mortality in men and women worldwide, where the most common subtype is pancreatic ductal adenocarcinoma (PDAC). To date, the pathogenesis of PDAC remains incompletely understood and the prognosis of PDAC is poor. In the present study, the expression of interleukin‑28 receptor α subunit (IL‑28RA) in PDAC tissues was detected using immunofluorescence staining and western blotting. IL‑28RA recombinant plasmids and control pCMV6‑entrymammalian expression plasmid, short hairpin (sh)IL‑28RA plasmids and control pRS scrambled shRNA vector purchased were used to produce stably transfected PANC‑1 cells overexpressing IL‑28RA or with IL‑28RA expression knocked down. MTS assays were used to measure cell viability and wound healing assay was used to assess the cell migratory ability in vitro. Flow cytometry analysis was performed to determine the proportion of cells in each phase of the cell cycle whereas total protein and phosphorylated protein levels were assessed using western blotting. Xenograft models of subcutaneous tumors were established by injecting PANC‑1 cells hypodermically into nude mice to investigate the effect of IL‑28RA on tumorigenesis and tumor growth. The results showed that the expression of IL‑28RA in PDAC tissues was lower compared with that in normal tissues. IL‑28RA overexpression in vitro resulted in the activation of the IL‑28RA pathway, which reduced cell viability and decreased the proportion of cells in the G₂/M phase by reducing cyclin B1 expression. In addition, IL‑28RA overexpression inhibited migration of PDAC cells. By contrast, an increased proportion of cells in G₂/M phase, upregulated cyclin B1 expression and enhanced cell viability and migratory ability along with inhibition of the IL‑28RA pathway were observed in PANC‑1 cells following IL‑28RA knockdown. The inhibitory effect of IL‑28RA was observed by tumor size in a nude mouse model induced by PANC‑1 cells with stable IL‑28RA overexpression or knockdown. The tumor size induced by PANC‑1 cells with stable IL‑28RA overexpression were smaller, whilst larger tumors induced by PANC‑1 cells were observed following stable IL‑28RA knockdown, when compared to control. Further studies showed that the effect of IL‑28RA on PDAC cells was exerted by regulating the phosphorylation levels of STAT1 and AKT. In conclusion, lower IL‑28RA expression may contribute to the pathogenesis of PDAC, where results from the present may provide further insights into the progression of PDAC, in addition to highlighting potentially novel therapeutic targets for this disease.

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