miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma
miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma
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miR-21通过miR-21-PDCD4-Stat3通路调节人唾液腺样囊性癌的肿瘤进展
DOI：
10.1038/labinvest.2015.105
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发表时间：
2015-12-01
影响因子：
5
通讯作者：
Ling, Zhi-Qiang
中科院分区：
文献类型：
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作者：
Jiang, Lie-Hao;Ge, Ming-Hua;Ling, Zhi-Qiang
miR-21 是一种假定的肿瘤癌 miR，在各种肿瘤中经常过度表达 microRNA，它通过靶向肿瘤抑制基因与肿瘤进展相关。在本研究中，我们试图确定 miR-21 是否对唾液腺腺样囊性癌 (SACC) 的肿瘤进展有作用以及可能的机制。我们发现SACC中miR-21的表达水平显着高于正常唾液组织，并且在有转移的肿瘤中也高于无转移的肿瘤。在体外模型中使用抗miR-21抑制剂，miR-21的下调显着降低了SACC细胞的侵袭和迁移能力，而pre-miR-21则增加了SACC细胞的侵袭和迁移能力。为了探索 miR-21 调节侵袭和迁移的潜在机制，我们鉴定了一种 miR-21 直接靶基因，程序性细胞死亡 4 (PDCD4)，它与侵袭和转移有关。在转移性SACC-LM细胞中抑制miR-21显着增加PDCD4启动子的报告活性和PDCD4蛋白的表达。这随后导致 p-STAT3 蛋白的下调。 SACC标本中miR-21的表达水平分别与PDCD4蛋白的表达呈正相关，与p-STAT3蛋白的表达呈负相关，表明STAT3-miR-21-PDCD4通路在这些肿瘤中的潜在作用。 miR-21 的失调通过靶向 PDCD4 在肿瘤生长和侵袭中发挥重要作用。因此，抑制miR-21可能为晚期SACC患者的治疗提供潜在的方法。
miR-21, which is a putative tumor onco-miR and frequently overexpressed microRNA in various tumors, has been linked to tumor progression through targeting of tumor-suppressor genes. In this study, we sought to determine whether miR-21 has any role on tumor progression of salivary adenoid cystic carcinoma (SACC) and the possible mechanisms. We found that the level of miR-21 expression was significantly higher in SACC than that in normal salivary tissues, and it is also higher in tumors with metastasis than that without metastasis. Using an anti-miR-21 inhibitor in an in vitro model, downregulation of miR-21 significantly decreased the capacity of invasion and migration of SACC cells, whereas a pre-miR-21 increased the capacity of invasion and migration of SACC cells. To explore the potential mechanisms by which miR-21 regulate invasion and migration, we identified one direct miR-21 target gene, programmed cell death 4 (PDCD4), which has been implicated in invasion and metastasis. The suppression of miR-21 in metastatic SACC-LM cells significantly increased the report activity of PDCD4 promoter and the expression of PDCD4 protein. This subsequently resulted in downregulation of the p-STAT3 protein. The level of miR-21 expression positively related to the expression of PDCD4 protein and negatively related to the expression of p-STAT3 protein in SACC specimens, respectively, indicating the potential role of the STAT3-miR-21-PDCD4 pathway in these tumors. Dysregulation of miR-21 has an important role in tumor growth and invasion by targeting PDCD4. Therefore, suppression of miR-21 may provide a potential approach for the treatment of advanced SACC patients.