Abstract

BackgroundCircular RNA (circRNA) plays an important role in regulating cell biological function and has been shown to be involved in cancer progression, including oral squamous cell carcinoma (OSCC). Circ-KIAA0907 has been found to play an anti-cancer role in OSCC, so it is worth exploring more functions and new mechanisms of circ-KIAA0907 in OSCC progression.MethodsQuantitative real-time PCR (qRT-PCR) was used to detect the expression of circ-KIAA0907, microRNA (miR)-96-5p, and unc-13 homolog C (UNC13C). Transwell assay, flow cytometry, and colony formation assay were employed to measure the migration, invasion, apoptosis, and radiosensitivity of cells. Besides, glucose uptake, lactate production, and extracellular acidification rate (ECAR) were determined to evaluate the glycolysis ability of cells. Dual-luciferase reporter assay and RIP assay were performed to confirm the interactions among circ-KIAA0907, miR-96-5p, and UNC13C. And RNA pull-down assay was used to verify the binding degree of miR-96-5p to its targets. Moreover, UNC13C protein level was examined using western blot (WB) analysis. OSCC xenograft models were constructed to perform in vivo experiments.ResultsCirc-KIAA0907 was a stability circRNA with lowly expression in OSCC. Overexpressed circ-KIAA0907 could inhibit migration, invasion, and glycolysis, while promoting apoptosis and radiosensitivity in OSCC cells. In the terms of mechanism, circ-KIAA0907 could sponge miR-96-5p to regulate UNC13C expression. MiR-96-5p overexpression could reverse the inhibitory effect of circ-KIAA0907 on OSCC progression, and UNC13C knockdown also could overturn the suppressive effect of miR-96-5p inhibitor on OSCC progression. Animal experiments revealed that circ-KIAA0907 could reduce the tumor growth of OSCC by regulating the miR-96-5p/UNC13C axis.ConclusionOur study suggests that circ-KIAA0907 restrains OSCC progression via the miR-96-5p/UNC13C axis, indicating that it may be a potential target for OSCC treatment.

Highlights

  • Oral squamous cell carcinoma (OSCC) mainly refers to a type of cancer that occurs in the epithelial tissue of oral mucosa [1, 2]

  • Our study aims to investigate the more functions of circ-KIAA0907 in oral squamous cell carcinoma (OSCC) development and explore the new mechanism of circKIAA0907 mediating OSCC progression through the hypothesis of Circular RNA (circRNA)/miRNA/mRNA axis

  • Circ-KIAA0907 is a downregulated circRNA in OSCC In 59 pairs of OSCC cancer tissues and adjacent normal tissues, we found that circ-KIAA0907 was significantly downregulated in OSCC cancer tissues (Fig. 1a)

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Summary

Introduction

Oral squamous cell carcinoma (OSCC) mainly refers to a type of cancer that occurs in the epithelial tissue of oral mucosa [1, 2]. It is urgent to explore OSCC pathogenesis and provide new ideas for OSCC treatment. With the in-depth research on circRNA function, more and more evidences show that circRNAs play a key role in cancer progression [10, 11]. Hsa_circ_100533 was discovered to be downregulated in OSCC, which played a negative role in OSCC proliferation and migration by sponging miR-933 to regulate GNAS [14]. Circular RNA (circRNA) plays an important role in regulating cell biological function and has been shown to be involved in cancer progression, including oral squamous cell carcinoma (OSCC). Circ-KIAA0907 has been found to play an anti-cancer role in OSCC, so it is worth exploring more functions and new mechanisms of circ-KIAA0907 in OSCC progression

Methods
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