MicroRNA‑519 inhibits hypoxia‑induced tumorigenesis of pancreatic cancer by regulating immune checkpoint PD‑L1

Nong,Kate; Zhang,Dong; Chen,Changze; Yang,Yue; Yang,Yong; Liu,Shengyong; Cai,Huihua

doi:10.3892/ol.2019.11234

MicroRNA‑519 inhibits hypoxia‑induced tumorigenesis of pancreatic cancer by regulating immune checkpoint PD‑L1

Authors:
- Kate Nong
- Dong Zhang
- Changze Chen
- Yue Yang
- Yong Yang
- Shengyong Liu
- Huihua Cai
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Affiliations: Department of Surgery of The Liver, Biliary Tract, and Pancreas, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, P.R. China
Published online on: December 20, 2019 https://doi.org/10.3892/ol.2019.11234
Pages: 1427-1433
Copyright: © Nong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic cancer is highly prevalent and exhibits a high incidence and mortality rate. Hypoxia contributes to tumorigenesis and the progression of pancreatic cancer. To the best of our knowledge, the role of microRNA (miR)‑519 has not been investigated in hypoxia‑induced pancreatic cancer progression. The purpose of the present study was to elucidate the mechanism underlying miR‑519‑mediated regulation of pancreatic cancer progression. Reverse transcription‑quantitative PCR and western blotting were performed to investigate miR‑519 and programmed death ligand 1 (PD‑L1) mRNA and protein levels, respectively. Additionally, a Transwell assay was performed to examine the invasiveness of PANC‑1 and SW1990 cells. Cells were subsequently stained with Annexin V to determine the apoptotic rate of cells. Furthermore, bioinformatics analysis and a dual‑luciferase reporter assay were performed to confirm the direct association between miR‑519 and PD‑L1, and a xenograft experiment was conducted to test the role of miR‑519 in vivo. The results revealed that the expression levels of miR‑519 in pancreatic cancer cells were reduced following hypoxia treatment. Furthermore, transfection with miR‑519 mimics inhibited PANC‑1 and SW1990 cell invasiveness, and induced apoptosis under hypoxic conditions. PD‑L1 was also identified as a downstream target of miR‑519, and rescued the miR‑519 mimic‑attenuated tumorigenesis of pancreatic cancer cells under hypoxic conditions. Additionally, treatment with miR‑519 mimics significantly suppressed the tumor growth of PANC‑1 cells. The results of the present study indicated a novel mechanism of miR‑519‑mediated tumorigenesis in pancreatic cancer cells under hypoxic conditions. The conclusions may be crucial for the improvement of future pancreatic cancer treatment.

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