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Circ_0001421 facilitates glycolysis and lung cancer development by regulating miR-4677-3p/CDCA3

Authors
  • Zhang, Koudong1
  • Hu, Hang1
  • Xu, Juan1
  • Qiu, Limin2
  • Chen, Haitao2
  • Jiang, Xingzhi1
  • Jiang, Yongqian1
  • 1 The Fourth Affiliated Hospital of Nantong University; The First People’s Hospital of Yancheng, No.66 Renmin South Road, Yancheng, Jiangsu, 224000, China , Yancheng (China)
  • 2 The Fourth Affiliated Hospital of Nantong University; The First People’s Hospital of Yancheng, Yancheng, Jiangsu, 224000, China , Yancheng (China)
Type
Published Article
Journal
Diagnostic Pathology
Publisher
BioMed Central
Publication Date
Oct 28, 2020
Volume
15
Issue
1
Identifiers
DOI: 10.1186/s13000-020-01048-1
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundLung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung. Circular RNAs (circRNAs) are proved to be key regulators of tumor progression. However, the regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear.MethodsThe expression levels of circ_0001421, microRNA-4677-3p (miR-4677-3p) and cell division cycle associated 3 (CDCA3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), Transwell and Tumor formation assays were performed to explore the role of circ_0001421 in LC. Glucose consumption and lactate production were examined by a Glucose assay kit and a Lactic Acid assay kit. Western blot was utilized to examine the protein levels of Hexokinase 2 (HK2) and CDCA3. The interaction between miR-4677-3p and circ_0001421 or CDCA3 was confirmed by dual-luciferase reporter assay.ResultsCirc_0001421 was increased in LC tissues and cells, and knockdown of circ_0001421 repressed cell proliferation, migration, invasion and glycolysis in vitro. Meanwhile, circ_0001421 knockdown inhibited LC tumor growth in vivo. Mechanistically, circ_0001421 could bind to miR-4677-3p, and CDCA3 was a target of miR-4677-3p. Rescue assays manifested that silencing miR-4677-3p or CDCA3 overexpression reversed circ_0001421 knockdown-mediated suppression on cell proliferation, migration, invasion and glycolysis in LC cells.ConclusionCirc_0001421 promoted cell proliferation, migration, invasion and glycolysis in LC by regulating the miR-4677-3p/CDCA3 axis, which providing a new mechanism for LC tumor progression.

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