Wang Xiaoming, Lu Xiubo, Geng Zushi, Yang Guoyu, Shi Yang
Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zheng Zhou, China.
Key Laboratory on Thyroid Tumor of Zhengzhou, Zhengzhou, China.
J Cell Biochem. 2017 Dec;118(12):4745-4752. doi: 10.1002/jcb.26142. Epub 2017 Jun 22.
The distance metastases of papillary thyroid carcinoma (PTC) were a major threaten for PTC patients, thus, to study the potential mechanism for the treatment of PTC was essential. Previous studies have shown that PTCSC3 (Thyroid Carcinoma Susceptibility Candidate 3), miR-574-5p and Wnt/β-catenin were involved in PTC, but the potential pathogenic mechanism among them was still unclear. Real-time PCR and Western blot were used to detect genes expression. Luciferase reporter assay was used to detect the combination of miR-574-5p and suppressor of cancer cell invasion (SCAI), as well as the ratio of TOP/FOP. RNA Pull-down assay verified the bound of PTCSC3 and miR-574-5p. MTT assay, Transwell assay, and wound scratch assay were used to detect cell viability and cell migration. The expression of PTCSC3 and SCAI were decreased, while miR-574-5p and β-catenin were increased in PTC tissues and cells. Overexpressed PTCSC3 suppressed cell proliferation and migration, promoted the expression of SCAI, but inhibited β-catenin. PTCSC3 absorbed miR-574-5p, and miR-574-5p targeted to SCAI; SCAI could regulate the activity of Wnt/β-catenin. PTCSC3/miR-574-5p regulated the activity of Wnt/β-catenin via SCAI and mediated cell proliferation and migration of PTC-1. In vivo experiments verified the fact that overexpressed PTCSC3 inhibited tumor growth. The signaling PTCSC3-miR-574-5p-SCAI-Wnt/β-catenin mediated the proliferation and migration of PTC-1 cells, which was vital for the further PTC therapy and prognosis. J. Cell. Biochem. 118: 4745-4752, 2017. © 2017 Wiley Periodicals, Inc.
甲状腺乳头状癌(PTC)的远处转移是PTC患者面临的主要威胁,因此,研究PTC的潜在治疗机制至关重要。以往研究表明,PTCSC3(甲状腺癌易感候选基因3)、miR-574-5p和Wnt/β-连环蛋白与PTC有关,但它们之间潜在的致病机制仍不清楚。采用实时荧光定量PCR和蛋白质免疫印迹法检测基因表达。荧光素酶报告基因检测法用于检测miR-574-5p与癌细胞侵袭抑制因子(SCAI)的结合以及TOP/FOP比值。RNA下拉实验验证了PTCSC3与miR-574-5p的结合。采用MTT法、Transwell法和划痕实验检测细胞活力和细胞迁移。在PTC组织和细胞中,PTCSC3和SCAI的表达降低,而miR-574-5p和β-连环蛋白的表达升高。过表达PTCSC3可抑制细胞增殖和迁移,促进SCAI的表达,但抑制β-连环蛋白。PTCSC3吸附miR-574-5p,且miR-574-5p靶向SCAI;SCAI可调节Wnt/β-连环蛋白的活性。PTCSC3/miR-574-5p通过SCAI调节Wnt/β-连环蛋白的活性,并介导PTC-1细胞的增殖和迁移。体内实验证实过表达PTCSC3可抑制肿瘤生长。PTCSC3-miR-574-5p-SCAI-Wnt/β-连环蛋白信号通路介导了PTC-1细胞的增殖和迁移,这对PTC的进一步治疗和预后至关重要。《细胞生物化学杂志》118: 4745 - 4752, 2017。© 2017威利期刊公司