CircZNF609 promotes cell proliferation, migration, invasion, and glycolysis in nasopharyngeal carcinoma through regulati
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CircZNF609 promotes cell proliferation, migration, invasion, and glycolysis in nasopharyngeal carcinoma through regulating HRAS via miR‑338‑3p Zhonglu Liu1 · Feifei Liu1 · Fang Wang2 · Xin Yang1 · Wentao Guo1 Received: 5 January 2020 / Accepted: 23 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords circZNF609 · miR-338-3p · HRAS · Glycolysis · Nasopharyngeal carcinoma Abbreviations circZNF609 Circular RNA zinc finger protein 609 NPC Nasopharyngeal carcinoma Zhonglu Liu and Feifei Liu contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03894-5) contains supplementary material, which is available to authorized users. * Xin Yang [email protected] * Wentao Guo [email protected] 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
Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China
2
HRAS GTPase HRas ATP Adenosine triphosphate
Introduction Nasopharyngeal carcinoma (NPC) is a common head and neck cancer originating in the nasopharynx [1]. NPC has a distinct geographical pattern of incidence, which is widely prevalent in southern China, where 40% of the world’s new cases arise every ye
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