miR-214 regulates papillary thyroid carcinoma cell proliferation and metastasis by targeting PSMD10.
miR-214 regulates papillary thyroid carcinoma cell proliferation and metastasis by targeting PSMD10.
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DOI：
10.3892/ijmm.2018.3902
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发表时间：
2018-12
影响因子：
5.4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Liu F;Lou K;Zhao X;Zhang J;Chen W;Qian Y;Zhao Y;Zhu Y;Zhang Y
微小RNA（microRNAs，miRNAs）通过调节基因表达，在肿瘤的发生发展中发挥重要作用。本研究旨在探讨miR-214在甲状腺乳头状癌细胞增殖和转移中的作用及其分子机制。miR-214在甲状腺乳头状癌组织和细胞中表达显著下调，且与淋巴结转移、肿瘤大小和TNM分期显著相关。miR-214的上调可显著降低甲状腺乳头状癌细胞的增殖，促进细胞凋亡和细胞周期阻滞。相反，下调miR-214导致相反的效果。此外，miR-214模拟物显著降低甲状腺乳头状癌细胞的迁移和侵袭，这与基质金属肽酶（MMP）-2和MMP-9的表达水平降低相关。甲状腺乳头状癌细胞中miR-214表达的恢复降低了与上皮间质转化（EMT）相关的活性。此外，蛋白酶体26 S亚基非ATP酶10（PSMD 10）被预测为miR-214的靶点。实验结果表明，miR-214通过直接靶向PSMD 10的3′端非翻译区，负调控PSMD 10的表达。PSMD 10的敲低减少了乳头状甲状腺癌细胞克隆形成、迁移和侵袭，最可能是通过抑制糖原合成酶激酶（GSK）-3β/β-连环蛋白和AKT信号传导。miR-214和PSMD 10在甲状腺乳头状癌组织中的表达水平呈负相关。综上所述，这些数据表明miR-214可能是治疗甲状腺乳头状癌的候选靶点。
MicroRNAs (miRNAs) have important effects on cancer occurrence and development by adjusting gene expression. The aim of the present study was to examine the role of miR-214 in papillary thyroid carcinoma cell proliferation and metastasis, and its molecular mechanisms. miR-214 was demonstrated to be markedly downregulated in papillary thyroid carcinoma tissues and cells compared with normal, and this was significantly associated with lymph node metastasis, tumor size and TNM stage. Upregulation of miR-214 significantly decreased cell proliferation, and promoted cell apoptosis and cell cycle arrest in papillary thyroid carcinoma cell lines in vitro. By contrast, downregulation of miR-214 resulted in the opposite effects. In addition, miR-214 mimics significantly decreased papillary thyroid carcinoma cell migration and invasion, which was correlated with decreased expression levels of matrix metallopeptidase (MMP)-2 and MMP-9. Restoration of miR-214 expression in papillary thyroid carcinoma cells decreased the activities associated with epithelial-mesenchymal transition (EMT). Furthermore, proteasome 26S subunit non-ATPase 10 (PSMD10) was predicted to be a target of miR-214. Experimental results demonstrated that miR-214 negatively regulated PSMD10 expression by targeting its 3′ untranslated region directly. Knockdown of PSMD10 reduced papillary thyroid carcinoma cell clone formation, migration and invasion, most likely by repressing glycogen synthase kinase (GSK)-3β/β-catenin and AKT signaling. Finally, a negative correlation was observed between the expression levels of miR-214 and PSMD10 in papillary thyroid carcinoma tissues. Taken together, these data suggested that miR-214 might be a candidate target for the treatment of papillary thyroid carcinoma.
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影响因子：
--
作者：
Dong, Wei;Li, Baosheng;Fu, Chengrui
通讯作者：
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DOI：
10.1073/pnas.0812591106
发表时间：
2009-02-03
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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作者：
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