lncRNA DGCR 5/miR‑27a‑3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway

Li,Xianjie; Zhou,Shanxue; Fan,Tianyi; Feng,Xuefeng

doi:10.3892/ijmm.2020.4632

lncRNA DGCR 5/miR‑27a‑3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway

Authors:
- Xianjie Li
- Shanxue Zhou
- Tianyi Fan
- Xuefeng Feng
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Affiliations: Department of Hepatobiliary Surgery, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang 315020, P.R. China
Published online on: June 4, 2020 https://doi.org/10.3892/ijmm.2020.4632
Pages: 729-739
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA (lncRNA) DGCR5 has been identified as a tumor suppressor in several types of cancer. However, its biological functions in pancreatic cancer (PaCa) have not yet been fully elucidated. The present study was designed to investigate the role of lncRNA DGCR5 in the regulation of PaCa cell apoptosis. For this purpose, lncRNA DGCR5, miR‑27a‑3p and Bcl‑2/adenovirus E1B‑19kDa‑interacting protein 3 (BNIP3) expression levels were examined by reverse transcription‑quantitative (RT‑qPCR) and western blot analysis, respectively. RNA pull‑down assay was used to verify DGCR5 as a target of miR‑27a‑3p and dual luciferase reporter assay was used to clarify whether miR‑27a‑3p targets the BNIP3 3' UTR. In addition, PaCa cell apoptosis was assessed by flow cytometry. Recombinant plasmids and cell transfection were performed to modulate the endogenous expression of related genes. Thereafter, the role of DGCR5 in PaCa was analyzed using a nude mouse model of PaCa. lncRNA DGCR5 was found to be downregulated in PaCa tissues and cells. DGCR5 functioned as a decoy of miR‑27a‑3p, and BNIP3 was negatively regulated by miR‑27a‑3p. Following the transfection of DGCR5 plasmid into PaCa cells, the expression of miR‑27a‑3p was downregulated, and this downregulation was reversed following transfection with miR‑27a‑3p mimic. In addition, DGCR5 regulated the BNIP3 and p38 MAPK pathways via miR‑27a‑3p and promoted PaCa cell apoptosis via the miR‑27a‑3p/BNIP3 pathway. The results of in vivo experiments also indicated the positive effects of DGCR5 on a nude mouse model of PaCa. On the whole, the findings of the present study indicate that lncRNA DGCR5 upregulates the BNIP3 and p38 MAPK pathways via miR‑27a‑3p to promote PaCa cell apoptosis, thereby attenuating PaCa development.

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