Department of Radiotherapy, the First Affiliated Hospital of Zhengzhou University, Zhengdong Branch, Zhengzhou, 475000, Henan Province, People's Republic of China.
J Exp Clin Cancer Res. 2019 Feb 21;38(1):97. doi: 10.1186/s13046-019-1023-4.
Epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis with the involvement of microRNAs (miRNAs). This study aims to assess the role of miR-506 working in tandem with LIM Homeobox 2 (LHX2) in EMT and metastasis through the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma (NPC).
Differentially expressed genes associated with NPC were screened using microarray analyses, from which LHX2 was identified. Next, the potential relationship between miR-506 and LHX2 was analyzed. In order to explore the effect of miR-506 or LHX2 on NPC cell proliferation, migration, invasion and apoptosis, serials of mimics, inhibitors or siRNA against LHX2 were transfected into NPC cells. Then, the expression patterns of LHX2, Wnt1, β-catenin, E-cadherin, Vimentin, TCF4 and Twist were determined to assess the influence of miR-506 or LHX2 on EMT as well as the relationship between the Wnt/β-catenin signaling pathway and TCF4. The tumorigenicity and lymph node metastasis (LNM) in xenograft tumors of nude mice were observed.
The has-miR-506-3p was identified as the down-regulated gene in NPC based on the microarray data while LHX2 was negatively regulated by miR-506. Over-expression of miR-506 or silencing of LHK2 inhibited NPC cell proliferation, migration, invasion, tumorigenicity and LNM but promoted apoptosis indicated by decreased Wnt1, β-catenin, Vimentin, TCF4 and Twist expressions along with increased E-cadherin expressions.
miR-506 inhibits tumor growth and metastasis in NPC via inhibition of Wnt/β-catenin signaling by down-regulating LHX2, accompanied by decreased TCF4. Taken together, miR-506 targeted-inhibition LHX2 presents a promising therapeutic strategy for the treatment of NPC.
ChiCTR1800018889 . Registered 15 October 2018.
上皮-间充质转化（EMT）相关蛋白通过 microRNAs（miRNAs）在癌症进展和转移中发挥关键作用。本研究旨在评估 miR-506 与 LIM 同源盒 2（LHX2）在鼻咽癌（NPC）中通过 Wnt/β-catenin 信号通路协同作用在 EMT 和转移中的作用。
通过微阵列分析筛选与 NPC 相关的差异表达基因，其中鉴定出 LHX2。接下来，分析了 miR-506 与 LHX2 之间的潜在关系。为了探讨 miR-506 或 LHX2 对 NPC 细胞增殖、迁移、侵袭和凋亡的影响，将一系列针对 LHX2 的模拟物、抑制剂或 siRNA 转染到 NPC 细胞中。然后，确定 LHX2、Wnt1、β-catenin、E-cadherin、Vimentin、TCF4 和 Twist 的表达模式，以评估 miR-506 或 LHX2 对 EMT 的影响，以及 Wnt/β-catenin 信号通路与 TCF4 的关系。观察裸鼠异种移植瘤的致瘤性和淋巴结转移（LNM）。
基于微阵列数据，确定 has-miR-506-3p 为 NPC 下调基因，而 LHX2 受 miR-506 负调控。miR-506 的过表达或 LHK2 的沉默抑制 NPC 细胞增殖、迁移、侵袭、致瘤性和 LNM，但促进凋亡，表现为 Wnt1、β-catenin、Vimentin、TCF4 和 Twist 表达降低，E-cadherin 表达增加。
miR-506 通过下调 LHX2 抑制 NPC 中的 Wnt/β-catenin 信号，从而抑制肿瘤生长和转移，同时降低 TCF4。总之，miR-506 靶向抑制 LHX2 为 NPC 的治疗提供了一种有前途的治疗策略。
ChiCTR1800018889。注册于 2018 年 10 月 15 日。
