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CircZNF609 promotes cell proliferation, migration, invasion, and glycolysis in nasopharyngeal carcinoma through regulating HRAS via miR-338-3p

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Abstract

Circular RNA zinc finger protein 609 (circZNF609) has been reported to involve in nasopharyngeal carcinoma (NPC) tumorigenesis regulation. However, the role and the molecular mechanism of circZNF609 in NPC remain unclear. Levels of circZNF609, microRNA (miR)-338-3p, and GTPase HRas (HRAS) were detected by quantitative real-time polymerase chain reaction or Western blot. Cell proliferation, migration, and invasion were analyzed using cell counting kit-8 assay, colony formation assay, and transwell assay, respectively. Glucose metabolism was calculated by measuring glucose consumption, lactate production, adenosine triphosphate (ATP) levels, and HK2 activity. The interaction between miR-338-3p and circZNF609 or HRAS was analyzed by the dual-luciferase reporter assay. In vivo experiment was conducted using the murine xenograft model. CircZNF609 was elevated in NPC tissues and cell lines, and high circZNF609 expression had a poor prognosis. CircZNF609 knockdown suppressed NPC progression in vitro by inhibiting cell proliferation, migration, invasion, and glycolysis and hindered tumor growth in vivo. MiR-338-3p directly bound to circZNF609 and HRAS, and circZNF609 knockdown repressed NPC cell malignant properties by binding to miR-338-3p. MiR-338-3p was low in NPC, and miR-338-3p restoration performed anti-tumor effects in cells of NPC by targeting HRAS. Importantly, circZNF609 acted as a competing endogenous RNA of miR-338-3p to regulate HRAS. CircZNF609 knockdown suppressed cell tumorigenesis in NPC via regulating miR-338-3p/HRAS axis, suggesting a novel therapeutic strategy for NPC.

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Abbreviations

circZNF609:

Circular RNA zinc finger protein 609

NPC:

Nasopharyngeal carcinoma

HRAS:

GTPase HRas

ATP:

Adenosine triphosphate

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  1. Zhonglu Liu and Feifei Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuhuangding East Road, Zhifu District, Yantai, 264000, Shandong, China

    Zhonglu Liu, Feifei Liu, Xin Yang & Wentao Guo

  2. Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China

    Fang Wang

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  1. Zhonglu Liu
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Liu, Z., Liu, F., Wang, F. et al. CircZNF609 promotes cell proliferation, migration, invasion, and glycolysis in nasopharyngeal carcinoma through regulating HRAS via miR-338-3p. Mol Cell Biochem 476, 175–186 (2021). https://doi.org/10.1007/s11010-020-03894-5

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