Department of Stomatology, Jingmen No.1 People's Hospital, Jingmen City, China.
Oral Dis. 2023 Jul;29(5):1979-1990. doi: 10.1111/odi.14207. Epub 2022 May 27.
Accumulating articles have suggested the important regulatory roles of circular RNAs in human cancers, including oral squamous cell carcinoma (OSCC). However, the role of circ_0001971 in OSCC progression remains to be determined.
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays were conducted to analyze cell proliferation ability. Cell migration and invasion abilities were assessed by transwell assays. Dual-luciferase reporter assay was conducted to confirm the target relation between miR-107 and circ_0001971 or FZD4. Xenograft tumor model was established to analyze the biological role of circ_0001971 in regulating tumor growth in vivo.
Circ_0001971 was markedly up-regulated in OSCC tissues and cell lines. Circ_0001971 knockdown inhibited the growth of xenograft tumors in vivo. miR-107 was confirmed as a direct target of circ_0001971, and circ_0001971 depletion-mediated anti-tumor effects in OSCC cells could be largely alleviated by silencing miR-107. miR-107 directly targeted the 3' untranslated region of FZD4, and FZD4 overexpression largely reversed the anti-tumor effects of circ_0001971 in OSCC cells. Circ_0001971 could positively regulate FZD4 expression by targeting miR-107 in OSCC cells.
Circ_0001971 promoted the proliferation, migration, and glycolysis of OSCC cells through mediating miR-107/FZD4 axis. Circ_0001971 might be a new effective target for OSCC treatment in future.
越来越多的文章表明环状 RNA 在人类癌症中具有重要的调控作用,包括口腔鳞状细胞癌(OSCC)。然而,circ_0001971 在 OSCC 进展中的作用仍有待确定。
采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和集落形成实验分析细胞增殖能力。通过 Transwell 实验评估细胞迁移和侵袭能力。双荧光素酶报告实验证实 miR-107 与 circ_0001971 或 FZD4 之间的靶关系。建立异种移植肿瘤模型分析 circ_0001971 在体内调节肿瘤生长的生物学作用。
circ_0001971 在 OSCC 组织和细胞系中明显上调。circ_0001971 敲低抑制体内异种移植肿瘤的生长。miR-107 被证实为 circ_0001971 的直接靶标,circ_0001971 在 OSCC 细胞中的抑瘤作用可通过沉默 miR-107 而得到显著缓解。miR-107 可直接靶向 FZD4 的 3'非翻译区,FZD4 过表达可显著逆转 circ_0001971 在 OSCC 细胞中的抑瘤作用。circ_0001971 可通过靶向 miR-107 在 OSCC 细胞中正向调节 FZD4 表达。
circ_0001971 通过介导 miR-107/FZD4 轴促进 OSCC 细胞的增殖、迁移和糖酵解。circ_0001971 可能成为未来 OSCC 治疗的一个新的有效靶点。