miR-3619-3p promotes papillary thyroid carcinoma progression via Wnt/beta-catenin pathway
miR-3619-3p promotes papillary thyroid carcinoma progression via Wnt/beta-catenin pathway
复制标题
miR-3619-3p通过Wnt/β-catenin通路促进甲状腺乳头状癌进展
DOI：
10.21037/atm.2019.10.71
复制
发表时间：
2019
影响因子：
--
通讯作者：
Xiao Haipeng
中科院分区：
文献类型：
--
作者：
Yu Shuang;Cao Siting;Hong Shubin;Lin Xiaorong;Guan Hongyu;Chen Shuwei;Zhang Quan;Lv Weiming;Li Yanbing;Xiao Haipeng
背景
众所周知，微小RNA（microRNAs，miRNAs）在甲状腺乳头状癌（papillary thyroid carcinoma，PTC）中表达异常，但其在PTC发生发展和转移中的作用尚不清楚。microRNA-3619- 3 p（miR-3619- 3 p）作为一种癌基因与癌症进展相关，预计其靶向Wnt/β-catenin信号通路。我们的研究旨在探讨miR-3619- 3 p对PTC细胞迁移和侵袭的作用以及潜在机制。
方法
采用实时荧光定量聚合酶链反应（qRT-PCR）检测miR-3619- 3 p在36例PTC组织及相应癌旁组织、3株PTC细胞系（BCPAP、K1、TPC-1）和正常甲状腺上皮细胞系（N-thy-ori 3-1）中的表达。分析miR-3619- 3 p表达与PTC患者临床病理状态的关系。迁移、侵袭和伤口愈合用于评估miR-3619- 3 p在PTC中的作用。Western blotting检测β-catenin的活化情况及可能的分子途径。
结果
miR-3619- 3 p在PTC组织中的表达显著高于癌旁组织（P<0. 01），其高表达与甲状腺外浸润、多中心性、颈淋巴结转移呈正相关。此外，与N-thy-ori 3-1相比，miR-3619- 3 p在PTC细胞系中也上调。MiR-3619- 3 p增强了PTC细胞系的迁移和侵袭能力。此外，miR-3619- 3 p通过维持β-catenin mRNA的稳定性激活Wnt/β-catenin通路。
结论
miR-3619- 3 p作为癌基因，通过增加β-catenin的稳定性激活Wnt/β-catenin通路，促进PTC细胞的迁移和侵袭。
Background
It is well known that the dysregulation of microRNAs (miRNAs) has been identified in papillary thyroid carcinoma (PTC), but their roles in the progression and metastasis of PTC remain unclear. MicroRNA-3619-3p (miR-3619-3p) is associated with cancer progression as an oncogene which is predicted to target at the Wnt/β-catenin signaling pathway. Our study aimed to investigate the role of miR-3619-3p on PTC cell migration and invasion, as well as the underlying mechanisms.
Methods
The expression of miR-3619-3p in 36 PTC tissues and corresponding tumor-adjacent tissues, as well as 3 PTC cell lines (BCPAP, K1, TPC-1) and the normal thyroid epithelial cell line (N-thy-ori 3-1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between miR-3619-3p expression and clinicopathologic status of PTC patients was analyzed. Migration, invasion, and wound healing, were used to evaluate the role of miR-3619-3p in PTC. The activation of β-catenin and the possible molecular pathway were detected by western blotting.
Results
The expression of miR-3619-3p in PTC tissues was significantly higher than the corresponding tumor-adjacent tissues (P<0.01), and its high expression positively correlated with extrathyroidal invasion, multicentricity, and cervical lymph node metastasis. Moreover, the miR-3619-3p was also up-regulated in PTC cell lines when compared to N-thy-ori 3-1. MiR-3619-3p enhanced the capabilities of migration and invasion in PTC cell lines. Furthermore, miR-3619-3p activated Wnt/β-catenin pathway via maintaining the mRNA stability of β-catenin.
Conclusions
miR-3619-3p promoted PTC cell migration and invasion as an oncogene via activating the Wnt/β-catenin pathway through increasing the stability of β-catenin.