Circ-PVT1/miR-106a-5p/HK2 axis regulates cell growth, metastasis and glycolytic metabolism of oral squamous cell carcino
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Circ‑PVT1/miR‑106a‑5p/HK2 axis regulates cell growth, metastasis and glycolytic metabolism of oral squamous cell carcinoma Xiaoyan Zhu1 · Juan Du2 · Zhiqiang Gu1 Received: 6 May 2020 / Accepted: 17 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Circ-PVT1 · Oral squamous cell carcinoma · miR-106a-5p · HK2
Introduction Oral squamous cell carcinoma (OSCC) is the most aggressive cancer type of oral cancers with the highest incidence and mortality rate [1]. OSCC usually appears in peoples older than 50 years of age with males more than females, but the incidence of OSCC in young adults (1–6%) seems to be increasing worldwide in recent years [2]. Tobacco use, alcohol consumption and human papillomavirus (HPV) infection have been considered as major risk factors of OSCC patients [3]. OSCC has the high metastatic possibility to other parts * Zhiqiang Gu [email protected] 1
Department of Oral Restoration, Qingdao Campus of Qilu Hospital of Shandong University, Shibei District, No. 758 Hefei Road, Qingdao 266000, Shandong, China
Disinfection Supply Center, Qingdao Municipal Hospital, Qingdao 266011, Shandong, China
2
of the body, such as lymph nodes [4], thyroid [5] and lung metastasis [6]. The patient survival was reduced in advanced and metast
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