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环状 RNA 0001971 通过靶向 miR-107/FZD4 轴促进口腔鳞状细胞癌的进展。

Circ_0001971 makes progress of oral squamous cell carcinoma by targeting miR-107/FZD4 axis.

机构信息

Department of Stomatology, Jingmen No.1 People's Hospital, Jingmen City, China.

出版信息

Oral Dis. 2023 Jul;29(5):1979-1990. doi: 10.1111/odi.14207. Epub 2022 May 27.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

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