MicroRNA-98-HMGA2-POSTN signal pathway reverses epithelial-to-mesenchymal transition in laryngeal squamous cell carcinoma
MicroRNA-98-HMGA2-POSTN signal pathway reverses epithelial-to-mesenchymal transition in laryngeal squamous cell carcinoma
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MicroRNA-98-HMGA2-POSTN信号通路逆转喉鳞状细胞癌上皮间质转化
DOI：
10.1016/j.biopha.2019.108998
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发表时间：
2019-09-01
影响因子：
7.5
通讯作者：
Zheng, Hongliang
中科院分区：
文献类型：
--
作者：
Zhu, Minhui;Zhang, Caiyun;Zheng, Hongliang
逆转上皮细胞向间质细胞转化（EMT）被认为是抑制肿瘤进展和治疗耐药的潜在途径。在这里，我们的目的是揭示新的机制，我们可以逆转EMT和抑制喉鳞状细胞癌（LSCC）的转移。我们发现miR-98在喉鳞状细胞癌标本和细胞系中均显著减少。miR-98过表达可抑制喉鳞癌EMT相关基因的表达，抑制喉鳞癌的侵袭转移行为，减少肺转移。在机制研究中，miR-98直接靶向HMGA 2介导EMT。si-RNA法敲低HMGA 2基因可降低多个EMT相关基因的表达，降低喉鳞癌的迁移和侵袭能力。与此同时，HMGA 2的过表达使喉鳞状细胞癌细胞转化为干细胞样特征。此外，我们揭示，HMGA 2介导的EMT是密切相关的表达POSTINK，抑制EMT，作为一种肿瘤抑制因子，通过基因分析。P001在转录上被HMGA 2抑制。在临床上，喉鳞癌患者组中HMGA 2 mRNA水平与miR-98水平呈负相关。总之，我们的研究提供了一个强大的信号：miR-98-HMGA-POR 4在LSCC中，它能够逆转EMT并抑制转移，强调了该信号的治疗潜力。
It has been widely considered that reversing epithelial-to-mesenchymal transition (EMT) is a potential access to restrain cancer progression and therapeutic resistance. Here, we aim to uncover the novel mechanisms by which we can reverse EMT and inhibit metastasis in laryngeal squamous cell carcinoma (LSCC). We show that miR-98 is significantly reduced in both LSCC specimens and cell lines. Over-expression of miR-98 inhibits the EMT-related gene expression and metastasis and invasive behavior in LSCC in vitro, as well as reduces lung metastasis in mouse model. In the mechanistically study, miR-98 directly targets HMGA2 in mediating EMT. HMGA2 knock down by si-RNA method declines several EMT-related genes expression and LSCC migration and invasion. In parallel, overexpression of HMGA2 transforms LSCC cells to acquire stem cell-like features. Furthermore, we reveal that HMGA2-mediated EMT is closely linked with the expression of POSTN that inhibits EMT, as a tumor suppressor, by gene profiling analyses. POSTN is transcriptionally repressed by HMGA2. In clinic, the HMGA2 mRNA level is negatively correlated with the miR-98 level in LSCC patient cohort. In conclusion, our study confers a powerful signal: miR-98-HMGA-POSTN in LSCC, which is able to reverse EMT and inhibit metastasis, underlining the therapeutic potential of this signal.