MiR-144-3p promotes the tumor growth and metastasis of papillary thyroid carcinoma by targeting paired box gene 8.

MiR-144-3p promotes the tumor growth and metastasis of papillary thyroid carcinoma by targeting paired box gene 8.
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DOI:
10.1186/s12935-018-0550-y
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发表时间:
2018
影响因子:
5.8
通讯作者:
Li G
Li G
中科院分区:
医学2区
文献类型:
--
作者:
Liu C;Su C;Chen Y;Li G

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PAX 8基因在甲状腺发育中表达,是甲状腺发育所必需的。MiR-144- 3 p在肿瘤中表达异常,可阻断靶基因的表达。本研究旨在了解MiR-144- 3 p在甲状腺乳头状癌(PTC)中的作用以及相关机制。采用实时荧光定量PCR、免疫组化和Western blot检测靶miRNA和/或基因的表达。CCK-8法检测细胞生长情况,流式细胞仪检测细胞周期进程,流式细胞仪检测细胞凋亡。荧光素酶报告基因检测miR-144- 3 p是否与PAX 8的3′非翻译区结合。我们发现PAX 8在PTC中减少,而miR-144- 3 p在PTC中增加。过表达miR-144- 3 p可促进细胞活力和细胞周期进程。miR-144- 3 p可调控细胞周期相关基因cyclin D1、cyclin-dependent kinase 2和CDC 25 A的表达。同时,miR-144- 3 p的存在或缺失均通过调节E-cadherin、N-cadherin和vimentin的表达影响PTC的上皮-间质转化。此外,PAX 8可能是miR-144- 3 p的潜在直接靶标。在机制上,细胞外信号调节激酶1/2、Akt和c-Jun N-末端激酶的激活可能与miR-144- 3 p的促肿瘤作用相关。此外,miR-144- 3 p的阻断迫使通过X射线暴露或紫杉醇递送的抗肿瘤作用。miR-144- 3 p通过靶向PAX 8促进PTC的生长和转移。本研究为PTC的预后判断提供了有价值的指标和治疗策略。
Paired box gene 8 (PAX8) is expressed in and indispensable to thyroid development. MiR-144-3p is found dys-regulated in cancers, and it can block the expression of target gens. This study sought to understand the effect of MiR-144-3p in papillary thyroid carcinoma (PTC) as well as the associated mechanisms. Real-time PCR, immunohistochemical and Western blot assays were performed to examine the expression of target miRNA and/or genes. CCK-8 and flow cytometry analysis was used to respectively test cell growth, cell cycle progression and apoptosis. Luciferase reporter assay was performed to find out whether miR-144-3p could bind to the 3′ untranslated region of PAX8 or not. We found that PAX8 decreased in PTC, while miR-144-3p increased in PTC. Over-expression of miR-144-3p promoted the cell viability and cell cycle progression. The expressions of cell-cycle-related genes, cyclin D1, cyclin-dependent kinase 2 and CDC25A were modulated by miR-144-3p. Meanwhile, the presence or absence of miR-144-3p both affected epithelial-mesenchymal transition of PTC by regulating the expression of E-cadherin, N-cadherin and vimentin. Moreover, PAX8 may be a potential direct target of miR-144-3p. Mechanically, the activation of extracellular signal–regulated kinases 1/2, Akt and c-Jun N-terminal kinases may be associated with the tumor-promoting effect of miR-144-3p. In addition, the blockage of miR-144-3p forced the anti-tumor effect delivered by X-ray exposure or paclitaxel. MiR-144-3p promoted the growth of tumor and the metastasis of PTC by targeting PAX 8. The study provided promising prognosis markers and valuable treatment strategy for PTC.
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