Department of Stomatology, The Second Affiliated Hospital of Mudanjiang Medical College, No. 15, Dongxiaoyun Street, Aimin District, Mudanjiang, 157000, Heilongjiang Province, China.
Department of General Surgery, The Second Affiliated Hospital of Mudanjiang Medical College, Mudanjiang, 157000, Heilongjiang Province, China.
World J Surg Oncol. 2021 Mar 14;19(1):75. doi: 10.1186/s12957-021-02184-8.
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.
Quantitative 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.
Circ-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.
Our 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.
环状 RNA（circRNA）在调节细胞生物学功能方面发挥着重要作用，并且已经证明其参与了癌症的进展，包括口腔鳞状细胞癌（OSCC）。circ-KIAA0907 已被发现在 OSCC 中发挥抗癌作用，因此值得进一步探索 circ-KIAA0907 在 OSCC 进展中的更多功能和新机制。
采用实时定量 PCR（qRT-PCR）检测 circ-KIAA0907、微小 RNA（miR）-96-5p 和 unc-13 同源物 C（UNC13C）的表达。采用 Transwell 检测、流式细胞术和集落形成实验来测量细胞的迁移、侵袭、凋亡和放射敏感性。此外，通过测定葡萄糖摄取、乳酸生成和细胞外酸化率（ECAR）来评估细胞的糖酵解能力。通过双荧光素酶报告基因实验和 RIP 实验来证实 circ-KIAA0907、miR-96-5p 和 UNC13C 之间的相互作用。采用 RNA 下拉实验来验证 miR-96-5p 与其靶标的结合程度。此外，采用 Western blot（WB）分析检测 UNC13C 蛋白水平。构建 OSCC 异种移植模型进行体内实验。
circ-KIAA0907 是一种低表达的稳定性 circRNA，在 OSCC 中表达下调。过表达 circ-KIAA0907 可抑制 OSCC 细胞的迁移、侵袭和糖酵解，同时促进细胞凋亡和放射敏感性。从机制上讲，circ-KIAA0907 可通过海绵吸附 miR-96-5p 来调节 UNC13C 的表达。过表达 miR-96-5p 可逆转 circ-KIAA0907 对 OSCC 进展的抑制作用，而 UNC13C 敲低也可推翻 miR-96-5p 抑制剂对 OSCC 进展的抑制作用。动物实验表明，circ-KIAA0907 通过调节 miR-96-5p/UNC13C 轴可减少 OSCC 肿瘤的生长。
本研究表明，circ-KIAA0907 通过 miR-96-5p/UNC13C 轴抑制 OSCC 进展，表明其可能成为 OSCC 治疗的潜在靶点。
