Cancer Management and Research (Oct 2020)

Circ_0032821 Facilitates Gastric Cancer Cell Proliferation, Migration, Invasion and Glycolysis by Regulating MiR-1236-3p/HMGB1 Axis

  • Chen L,
  • Chi K,
  • Xiang H,
  • Yang Y

Journal volume & issue
Vol. Volume 12
pp. 9965 – 9976

Abstract

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Lei Chen,1 Kun Chi,2 Huaguo Xiang,3 Yan Yang4 1Department of Emergency Medicine, Xiang’an Hospital of Xiamen University, Xiamen, 361101, People’s Republic of China; 2Department of Nursing, Qingdao Municipal Hospital (Group), Qingdao 266071, People’s Republic of China; 3Medical Laboratory, Shenzhen Baoan District Fuyong People’s Hospital, Shenzhen 518103, People’s Republic of China; 4Department of Gastroenterology, Central People’s Hospital of Tengzhou, Tengzhou 277500, People’s Republic of ChinaCorrespondence: Yan YangDepartment of Gastroenterology, Central People’s Hospital of Tengzhou, Tengzhou, Shandong 277500, People’s Republic of ChinaEmail [email protected]: Circular RNAs (circRNAs) play an essential role in the pathogenesis of malignant tumors, including gastric cancer (GC). However, the effect of circ_0032821 on GC remains largely unknown.Methods: QRT-PCR assay was employed to examine the levels of circ_0032821, CEP128 mRNA and miR-1236-3p. RNase R digestion assay was utilized to verify the feature of circ_0032821. Cell Counting Kit-8 (CCK-8) assay and transwell assay were adopted to evaluate cell proliferation and metastasis. The level of glycolysis was evaluated through detecting ECAR, OCR, lactate production, glucose uptake and ATP synthesis. Dual-luciferase reporter assay and RIP assay were conducted to analyze the relationship between miR-1236-3p and circ_0032821 or HMGB1. Western blot assay was adopted for high mobility group box 1 (HMGB1) level. Murine xenograft model assay was utilized for the effect of circ_0032821 in vivo.Results: High level of circ_0032821 was observed in GC tissues and cells. Silencing of circ_0032821 markedly repressed cell proliferation, metastasis and glycolysis in GC cells in vitro and blocked tumorigenesis of GC in vivo. For mechanism analysis, circ_0032821 was identified as the sponge of miR-1236-3p and HMGB1 was the target gene of miR-1236-3p. Moreover, miR-1236-3p suppression restored the influences of circ_0032821 deficiency on GC cell proliferation, metastasis and glycolysis. Overexpression of miR-1236-3p relieved the malignant behaviors of GC cells by targeting HMGB1.Conclusion: Circ_0032821 accelerated GC development through elevating HMGB1 expression via sponging miR-1236-3p.Keywords: gastric cancer, circ_0032821, miR-1236-3p, HMGB1

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