Department of General Surgery, the First People's Hospital of Yancheng, Yancheng, Jiangsu Province, 224005, PR China.
Department of General Surgery, the People's Hospital of Dafeng Yancheng, Yancheng, Jiangsu Province, 224100, PR China.
Tissue Cell. 2021 Dec;73:101647. doi: 10.1016/j.tice.2021.101647. Epub 2021 Sep 10.
MiR-200c has been reported in several types of human cancer. Nevertheless, the expression profile and biological functions of miR-200c remain uncovered papillary thyroid cancer (PTC). The expression level of miR-200c was evaluated in PTC tissues using RT-qPCR. Survival analysis was performed in a cohort of 88 PTC patients. The effects of miR-200c on cell proliferation, migration, and invasion capacities were analyzed using CCK-8 and transwell assays. Target genes of miR-200c were assessed using luciferase reporter assay, RT-qPCR, Western blot and rescue experiments. MiR-200c was found to be upregulated in human PTC tissues and closely associated with pN stage and distant metastasis. High expression of miR-200c was associated with poor clinical prognosis in PTC patients. Whilst overexpression of miR-200c was demonstrated to promote the proliferation, migration, and invasion of PTC cells; knockdown of miR-200c showed an opposite inhibitory effect. Bioinformatics analysis and luciferase reporter assays confirmed that PTEN is a downstream target of miR-200c. Functional assays demonstrated that PTC cell proliferation, migration, and invasion were promoted by miR-200c via negative regulation of PTEN. Finally, overexpression of PTEN was shown to partially reverse the tumor promoting effect of miR-200c. In conclusion, this study indicates that miR-200c is a crucial prognostic biomarker of PTC, and that targeting of miR-200c/ PTEN axis may be of therapeutic significance in PTC patients.
miR-200c 在几种人类癌症中已有报道。然而，miR-200c 在甲状腺乳头状癌（PTC）中的表达谱和生物学功能仍未被揭示。本研究采用 RT-qPCR 检测 PTC 组织中 miR-200c 的表达水平。对 88 例 PTC 患者进行生存分析。采用 CCK-8 和 Transwell 实验分析 miR-200c 对细胞增殖、迁移和侵袭能力的影响。利用荧光素酶报告实验、RT-qPCR、Western blot 和挽救实验评估 miR-200c 的靶基因。结果发现 miR-200c 在人 PTC 组织中上调，与 pN 分期和远处转移密切相关。miR-200c 高表达与 PTC 患者的不良临床预后相关。过表达 miR-200c 可促进 PTC 细胞的增殖、迁移和侵袭；而 miR-200c 的敲低则表现出相反的抑制作用。生物信息学分析和荧光素酶报告实验证实，PTEN 是 miR-200c 的下游靶基因。功能实验表明，miR-200c 通过负调控 PTEN 促进 PTC 细胞的增殖、迁移和侵袭。最后，过表达 PTEN 部分逆转了 miR-200c 的促肿瘤作用。综上所述，本研究表明 miR-200c 是 PTC 的重要预后生物标志物，靶向 miR-200c/PTEN 轴可能对 PTC 患者具有治疗意义。
