Esomeprazole affects the proliferation, metastasis, apoptosis and chemosensitivity of gastric cancer cells by regulating lncRNA/circRNA-miRNA-mRNA ceRNA networks

Qian Xu; Xiyun Jia; Qian Wu; Lei Shi; Zihan Ma; Nan Ba; Han Zhao; Xingzhou Xia; Zisen Zhang

doi:10.3892/ol.2020.12193

Esomeprazole affects the proliferation, metastasis, apoptosis and chemosensitivity of gastric cancer cells by regulating lncRNA/circRNA-miRNA-mRNA ceRNA networks

Oncol Lett. 2020 Dec;20(6):329. doi: 10.3892/ol.2020.12193. Epub 2020 Oct 6.

Authors

Qian Xu¹, Xiyun Jia¹, Qian Wu², Lei Shi³, Zihan Ma¹, Nan Ba¹, Han Zhao¹, Xingzhou Xia⁴, Zisen Zhang¹

Affiliations

¹ Department of Oncology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
² Department of Gastroenterology, Huanghe Central Hospital, Zhengzhou, Henan 450003, P.R. China.
³ Department of Clinical Pharmacy, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
⁴ Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

Abstract

Recently, proton pump inhibitors have become a hot research topic in the field of cancer drug research. However, the specific anti-tumor effect and underlying mechanisms of esomeprazole (ESO) in gastric cancer (GC) have remained elusive. In the present study, the toxic effects of ESO on the GC cell line AGS were investigated. MTT assays confirmed that ESO inhibited the proliferation of AGS cells and significantly enhanced their chemosensitivity. Transwell assays were performed to determine the anti-metastatic effects of ESO in AGS cells. Flow cytometry demonstrated that ESO induced cell apoptosis and caused cell cycle arrest in the S and G2/M phases. Furthermore, the differential expression of 948 long non-coding RNAs (lncRNAs), 114 circular RNAs (circRNAs), 1,197 mRNAs and 199 microRNAs (miRNAs) was detected in AGS cells via microarray analysis and RNA-sequencing. The top 10 differently expressed genes were mostly located on chromosomes 10 and 19. In addition, Gene Ontology analysis indicated that the genes were accumulated in functional terms associated with DNA replication, the cell cycle and the apoptotic signaling pathway. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed a variety of significantly dysregulated signaling pathways and targets, including the EGFR tyrosine kinase inhibitor resistance pathway, forkhead box O signaling pathway, p53 signaling pathway and platinum drug resistance pathway. Subsequently, the interactions of microtubule-associated protein 2 (MAP2), homeodomain-interacting protein kinase 2 (HIPK2) and ankyrin 2 (ANK2) were noted in a competing endogenous RNA (ceRNA) network, which may be important targets of ESO, exerting an anti-tumor effect in AGS cells. Collectively, ESO affects the proliferation, metastasis, apoptosis and chemosensitivity of gastric cancer cells by regulating long non-coding RNA/circRNA-miRNA-mRNA ceRNA networks.

Keywords: apoptosis; chemosensitivity; competing endogenous RNA; esomeprazole; gastric cancer; metastasis; proliferation.