Shi Dongliang, Wang Haiyan, Ding Mingjian, Yang Meng, Li Chenhao, Yang Wenhua, Chen Liang
Department of Surgical Oncology, Cangzhou Central Hospital, Cangzhou City, Hebei Province 061000, People's Republic of China.
Department of Radiation Oncology, Cangzhou Central Hospital, Cangzhou City, Hebei Province 061000, People's Republic of China.
Onco Targets Ther. 2019 Aug 16;12:6605-6616. doi: 10.2147/OTT.S205994. eCollection 2019.
Thyroid cancer (TC) is considered as the fastest growing malignancy in the human endocrine system, particularly papillary thyroid cancer (PTC). MicroRNAs (miRs) serve as a role in promoting or suppressing tumors in various types of malignant tumor including PTC. This study aims to explore whether microRNA-26a-5p (miR-26a-5p) could affect the proliferation, invasion and metastasis ability of PTC cells by regulating Wnt5a.
The expression of miR-26a-5p was examined by qRT-PCR in PTC tissue samples (58 cases, mean age 53 years old) and PTC cell lines (K1 and BCPAP). Cell proliferation, invasion and migration were tested with CCK8 assay, colony formation assay, transwell invasion assay and wound healing assay, respectively. Luciferase reporting experiment was used to verify that Wnt5a is a molecular target of miR-26a-5p. The relationship between miR-26a-5p and Wnt5a was analyzed by qRT-PCR and Western blot and was further proved by Pearson's correlation analysis. Animal (24 nude mice) experiments were used to demonstrate that miR-26a-5p inhibits tumor growth by targeting Wnt5a.
The expression of miR-26a-5p declined in PTC tissues (<0.01). The expression of miR-26a-5 was also significantly down-regulated in PTC tissues with advanced TNM stages (<0.01) and lymph node metastasis (<0.01) compared with normal thyroid tissues. Compared with normal human thyroid cell line Nthy-ori 3-1, the expression of miR-26a-5p in K1 cells and BCPAP cells were nearly 4.02-fold (<0.01) and 2.51-fold (<0.01) reduced. Up regulation of miR-26a-5p inhibited proliferation, colony formation, invasion and migration of PTC cells. MiR-26a-5p negatively regulated Wnt5a expression (=-0.887, <0.01), yet Wnt5a overexpression reversed the tumor-suppressive effect of miR-26a-5p in PTC. Animal experiments further verified that miR-26a-5p inhibited PTC growth by targeting Wnt5a.
Overexpression of miR-26a-5p depresses proliferation, invasion, metastasis of PTC via Wnt5a. Therefore, miR-26a-5p may represent a potentially effective target gene for PTC.
甲状腺癌（TC）被认为是人类内分泌系统中增长最快的恶性肿瘤，尤其是乳头状甲状腺癌（PTC）。微小RNA（miRs）在包括PTC在内的各种恶性肿瘤的肿瘤促进或抑制中发挥作用。本研究旨在探讨微小RNA-26a-5p（miR-26a-5p）是否可通过调节Wnt5a影响PTC细胞的增殖、侵袭和转移能力。
采用qRT-PCR检测58例PTC组织样本（平均年龄53岁）和PTC细胞系（K1和BCPAP）中miR-26a-5p的表达。分别用CCK8法、集落形成试验、Transwell侵袭试验和伤口愈合试验检测细胞增殖、侵袭和迁移能力。采用荧光素酶报告实验验证Wnt5a是miR-26a-5p的分子靶点。通过qRT-PCR和Western blot分析miR-26a-5p与Wnt5a的关系，并通过Pearson相关分析进一步证实。采用动物（24只裸鼠）实验证明miR-26a-5p通过靶向Wnt5a抑制肿瘤生长。
PTC组织中miR-26a-5p表达下降（<0.01）。与正常甲状腺组织相比，TNM分期较晚（<0.01）和有淋巴结转移（<0.01）的PTC组织中miR-26a-5的表达也显著下调。与正常人甲状腺细胞系Nthy-ori 3-1相比，K1细胞和BCPAP细胞中miR-26a-5p的表达分别降低了近4.02倍（<0.01）和2.51倍（<0.01）。miR-26a-5p上调抑制了PTC细胞的增殖、集落形成、侵袭和迁移。miR-26a-5p负向调节Wnt5a表达（=-0.887，<0.01），而Wnt5a过表达逆转了miR-26a-5p对PTC的肿瘤抑制作用。动物实验进一步证实miR-26a-5p通过靶向Wnt5a抑制PTC生长。
miR-26a-5p过表达通过Wnt5a抑制PTC的增殖、侵袭和转移。因此，miR-26a-5p可能是PTC的一个潜在有效靶基因。
