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Circ_0003159 upregulates LIFR expression through competitively binding to miR-221-3p/miR-222-3p to block gastric cancer development

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Abstract

Gastric cancer (GC) remains a major cause of cancer-related deaths. Increasing studies suggest that cancer development is accompanied by the deregulation of circular RNAs. We investigated the function of circ_0003159 in GC. The expression levels of circ_0003159, miR-221-3p/miR-222-3p and leukemia inhibitory factor receptor (LIFR) mRNA were measured by real-time quantitative polymerase chain reaction. Cell colony formation ability was assessed by colony formation assay, and cell viability was assessed by cell counting kit-8 assay. Cell apoptosis was assessed by flow cytometry assay and caspase3 activity. Cell migration and invasion were assessed by transwell assay. Glycolysis energy metabolism was assessed by 5’-triphosphate production, glucose uptake and lactate production. The protein levels of related marker proteins and LIFR were detected by western blot. The relationship between circ_0003159 and miR-221-3p/miR-222-3p, or LIFR and miR-221-3p/miR-222-3p was obtained from bioinformatics tools and verified by dual-luciferase reporter assay. A cancer tumorogenicity xenograft experiment in nude mice was conducted to determine the role of circ_0003159 in tumor growth by AGS cells. Our results showed that circ_0003159 expression was decreased in GC tissues and cells. Circ_0003159 overexpression sequestered GC cell viability, migration, invasion and glycolysis and induced cell apoptosis. MiR-221-3p and miR-222-3p were targets of circ_0003159, and the inhibition of miR-221-3p and miR-222-3p also blocked GC cell viability, migration, invasion and glycolysis and promoted cell apoptosis. LIFR was a common target of miR-221-3p and miR-222-3p. Interestingly, LIFR knockdown reversed the effects of circ_0003159 overexpression on GC cell behaviors. Circ_0003159 increased the expression level of LIFR by targeting miR-221-3p and miR-222-3p. The tumorigenicity assay showed that circ_0003159 overexpression inhibited tumor growth in vivo. In conclusion, circ_0003159 inhibited GC development in vitro and in vivo by enriching the level of LIFR via direct binding to miR-221-3p/miR-222-3p.

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Acknowledgements

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Funding

This study was supported by Natural Science Foundation of Inner Mongolia Autonomous Region [Grant No. 2018MS08050]; Baotou Medical College Yang Fan Project [Grant No. BYJJ-YF-2018028].

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  1. Liansheng Zheng and Boshi Yan contributed equally to this work.

Authors and Affiliations

  1. Department of Digestive Minimally Invasive Surgery, The Second Affiliated Hospital of Baotou Medical College, Baotou, China

    Liansheng Zheng, Boshi Yan, Guoliang Jin, Weijie Han, Hailong Wang, Zhepeng Wang & Yongqiang Ma

  2. Digestive Department, The Second Affiliated Hospital of Baotou Medical College, No. 30, Hudemulin Street, Qingshan District, Baotou, 014030, Inner Mongolia, China

    Yuanyuan Nian, Xianmei Meng & Zhenyu Jiang

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  1. Liansheng Zheng
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Zheng, L., Yan, B., Jin, G. et al. Circ_0003159 upregulates LIFR expression through competitively binding to miR-221-3p/miR-222-3p to block gastric cancer development. J Mol Histol 53, 173–186 (2022). https://doi.org/10.1007/s10735-021-10044-8

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