MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/-catenin signaling pathway by down-regulating LHX2 (Retracted Article)
MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/-catenin signaling pathway by down-regulating LHX2 (Retracted Article)
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DOI：
10.1186/s13046-019-1023-4
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发表时间：
2019-02-21
影响因子：
11.3
通讯作者：
Liu, Zhang-Suo
中科院分区：
文献类型：
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作者：
Liang, Tian-Song;Zheng, Ying-Juan;Liu, Zhang-Suo
背景上皮间质转化 (EMT) 相关蛋白在 microRNA (miRNA) 的参与下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 Homeobox2 (LHX2) 协同作用在鼻咽癌 (NPC) 中通过 Wnt/-catenin 信号通路进行 EMT 和转移的作用。 方法采用微阵列分析筛选与 NPC 相关的差异表达基因，从中鉴定出 LHX2。接下来，分析了 miR-506 和 LHX2 之间的潜在关系。为了探讨miR-506或LHX2对鼻咽癌细胞增殖、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转染鼻咽癌细胞。然后，测定LHX2、Wnt1、-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/-catenin信号通路与TCF4之间的关系。观察裸鼠异种移植瘤的致瘤性和淋巴结转移（LNM）。结果根据芯片数据，确定has-miR-506-3p为鼻咽癌中下调的基因，而LHX2则被miR-506负调控。过表达 miR-506 或沉默 LHK2 可抑制鼻咽癌细胞增殖、迁移、侵袭、致瘤性和 LNM，但会促进细胞凋亡，表现为 Wnt1、β-catenin、Vimentin、TCF4 和 Twist 表达减少以及 E-cadherin 表达增加。 结论 miR-506 通过下调 LHX2 抑制 Wnt/-catenin 信号传导，同时降低 E-cadherin 表达，从而抑制鼻咽癌肿瘤生长和转移。 TCF4。综上所述，miR-506靶向抑制LHX2为鼻咽癌的治疗提供了一种有前景的治疗策略。试验注册ChiCTR1800018889。注册日期：2018 年 10 月 15 日。
BackgroundEpithelial-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 Homeobox2 (LHX2) in EMT and metastasis through the Wnt/-catenin signaling pathway in nasopharyngeal carcinoma (NPC).MethodsDifferentially 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, -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/-catenin signaling pathway and TCF4. The tumorigenicity and lymph node metastasis (LNM) in xenograft tumors of nude mice were observed.ResultsThe 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, -catenin, Vimentin, TCF4 and Twist expressions along with increased E-cadherin expressions.ConclusionsmiR-506 inhibits tumor growth and metastasis in NPC via inhibition of Wnt/-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.Trial registrationChiCTR1800018889. Registered 15 October 2018.