Department of Stomatology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China.
Department of Hematology and Oncology, No. 988 Hospital of Joint Logistic Support Force of the Chinese People's Liberation Army, Zhengzhou, Henan, China.
Bioengineered. 2022 Jan;13(1):440-454. doi: 10.1080/21655979.2021.2009317.
Circ_0005320 was found to be elevated in oral squamous cell carcinoma (OSCC) and accelerated OSCC progression. Here, the potential mechanism of circ_0005320 in OSCC tumorigenesis was explored. The quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect the expression of circ_0005320, miR-486-3p, and miR-637. In vitro assays were conducted using cell counting kit-8, colony formation, transwell, angiogenesis, and flow cytometry assays. The targeting relationship between microRNA (miR)-486-3p and miR-637 or circ_0005320 was confirmed using the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway-related proteins were analyzed using Western blot. The murine xenograft model was established to perform in vivo assay. Circ_0005320 expression was higher in OSCC tissues and cells. Knockdown of circ_0005320 suppressed OSCC cell growth, migration, invasion, and induced cell apoptosis in vitro, as well as impeded tumor growth in vivo. Mechanistically, miR-486-3p or miR-637 were confirmed to be a target of circ_0005320. Moreover, the inhibitory effects of circ_0005320 silencing on OSCC growth were reversed by the inhibition of miR-486-3p or miR-637. We also found that circ_0005320-miR-486-3p/miR-637 axis mediated the activation of JAK2/STAT3 pathway. This study revealed a novel regulatory network of circ_0005320-miR-486-3p/miR-637 axis in OSCC progression, suggesting that circ_0005320 might be a potential biomarker and therapeutic target for OSCC.
环状 RNA（circRNA）0005320 在口腔鳞状细胞癌（OSCC）中升高并加速了 OSCC 的进展。本研究旨在探索 circ_0005320 在 OSCC 肿瘤发生中的潜在机制。使用实时定量聚合酶链反应（qRT-PCR）检测 circ_0005320、miR-486-3p 和 miR-637 的表达。通过细胞计数试剂盒-8（CCK-8）、集落形成、Transwell、血管生成和流式细胞术检测进行体外实验。使用双荧光素酶报告和 RNA 免疫沉淀（RIP）实验验证 miR-486-3p 和 miR-637 或 circ_0005320 之间的靶向关系。使用 Western blot 分析 Janus 激酶 2/信号转导和转录激活因子 3（JAK2/STAT3）通路相关蛋白。建立小鼠异种移植模型进行体内实验。结果显示，circ_0005320 在 OSCC 组织和细胞中表达较高。circ_0005320 敲低抑制 OSCC 细胞的生长、迁移和侵袭，并在体外诱导细胞凋亡，体内抑制肿瘤生长。机制上，miR-486-3p 或 miR-637 被证实是 circ_0005320 的靶基因。此外，circ_0005320 沉默对 OSCC 生长的抑制作用可被 miR-486-3p 或 miR-637 的抑制作用逆转。我们还发现，circ_0005320-miR-486-3p/miR-637 轴介导 JAK2/STAT3 通路的激活。本研究揭示了 circ_0005320-miR-486-3p/miR-637 轴在 OSCC 进展中的新调控网络，提示 circ_0005320 可能是 OSCC 的潜在生物标志物和治疗靶点。
