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Journal of Anesthesia & Pain Medicine(JAPM)

ISSN: 2474-9206 | DOI: 10.33140/JAPM

Impact Factor: 1.8

Hsa Circ 0000670 Regulates Cell Growth, Angiogenesis and Glutamine Metabolism of Gastric Cancer Cells Through Mir 141 3p/Alkbh1 Axis

Abstract

Jiajun Lu, Yuan Zhou, Zhiheng Chen, Honggang Jiang, Jin Li, Guangjian Dou

Background Gastric cancer (GC) is one of the four most deadly tumors in the world, and its occurrence is influenced by genetic and environmental factors. CircRNA-miRNA-mRNA is reported to be associated with variety cancer, including GC.

Methods The expression of hsa_circ_0000670, miR-141-3p and AlkB homolog 1 (ALKBH1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and apoptosis were detected by 5-Ethynyl2’-deoxyuridine (EdU) assay and flow cytometry. The protein expression levels were measured by western blot and immunohistochemistry (IHC). Tube forming experiment was performed to assess angiogenesis rate. The levels of glutamine and α-ketoglutaric acid (α-KG) were examined using commercial kits. The target interaction between miR-141-3p and circ_0000670 or ALKBH1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The effect of circ_0000670 on tumor in vivo was analyzed in mice.

Results Circ_0000670 had a stable ring structure and was accelerated in GC tissues and cells. The proliferation of GC was hampered by circ_0000670 knockdown in vivo and in vitro, and the apoptosis rate was increased by circ_0000670 knockdown. Circ_0000670 down-regulation suppressed angiogenesis, the level of glutamine and α-KG in GC cells. The impacts of circ_0000670 knockdown on GC were relieved by miR-141-3p inhibition. The results indicated that circ_0000670 silencing could induce cell proliferation decline in GC, which was ameliorated by miR-141-3p knockdown. The functions of miR-141-3p mimic on cell proliferation, apoptosis, angiogenesis, glutamine and α-KG were reversed by ALKBH1 up-regulation.

Conclusion Our findings revealed that circ_0000670 promoted GC progression though miR-141-3p and ALKBH1, suggesting that circ_0000670 might be a target for GC clinical treatment

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