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Circ-PVT1/miR-106a-5p/HK2 axis regulates cell growth, metastasis and glycolytic metabolism of oral squamous cell carcinoma

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Abstract

Oral squamous cell carcinoma (OSCC) is the most commonly diagnosed oral cavity malignancy. A handful of circular RNAs (circRNAs) have recently shown to act as crucial regulators in OSCC, including circRNA plasmacytoma variant translocation 1 (circ-PVT1). However, further exploration is still needed for the underlying functional mechanism behind circ-PVT1 in OSCC. The levels of circ-PVT1, microRNA-106a-5p (miR-106a-5p) and hexokinase II (HK2) were all examined applying with quantitative real-time polymerase chain reaction (qRT-PCR). Cellular analyses (cell viability, apoptosis, metastasis and glycolysis) in vitro were performed via cell counting kit-8 (CCK-8), flow cytometry, transwell migration/invasion assays and glycolysis-related indications (glucose consumption, lactate production and ATP/ADP ratio). HK2 protein level was measured through western blot. Dual-luciferase reporter assay was conducted to study the interplay between miR-106a-5p and circ-PVT1 or HK2. Xenografts in mice were used for analyzing circ-PVT1 in vivo. Circ-PVT1 was expressed with abnormal high level while miR-106a-5p was down-regulated in OSCC tissues and cells. Circ-PVT1 knockdown reduced OSCC cell growth, metastasis and glycolysis. Moreover, circ-PVT1 acted in OSCC by functioning as a miR-106a-5p sponge. HK2 was a target of miR-106a-5p and miR-106a-5p played an anti-tumor role in OSCC by inhibiting HK2. Furthermore, HK2 could be regulated by circ-PVT1 via targeting miR-106a-5p. In xenograft models of mice, down-regulation of circ-PVT1 retarded tumorigenesis via the miR-106a-5p/HK2 axis. Our works suggested that circ-PVT1 directly combined with miR-106a-5p to mediate HK2 level, consequently regulating cellular behaviors in OSCC as a tumor promoter.

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Authors and Affiliations

  1. Department of Oral Restoration, Qingdao Campus of Qilu Hospital of Shandong University, Shibei District, No. 758 Hefei Road, Qingdao, 266000, Shandong, China

    Xiaoyan Zhu & Zhiqiang Gu

  2. Disinfection Supply Center, Qingdao Municipal Hospital, Qingdao, 266011, Shandong, China

    Juan Du

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Zhu, X., Du, J. & Gu, Z. Circ-PVT1/miR-106a-5p/HK2 axis regulates cell growth, metastasis and glycolytic metabolism of oral squamous cell carcinoma. Mol Cell Biochem 474, 147–158 (2020). https://doi.org/10.1007/s11010-020-03840-5

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