miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma

作者：Liehao Jiang, Minghua Ge, Xiuxiu Hou, Jun Cao, Sisi Hu, Xiaoxiao Lu, Jing Han, Yichen Wu, Xiang Liu, Xin Zhu, Lian‐Lian Hong, Pei Li, Zhi‐Qiang Ling · 发表于：Laboratory Investigation · 年份：2015 · DOI：10.1038/labinvest.2015.105 · 被引用次数：54 · 研究领域：Cancer-related molecular mechanisms research、MicroRNA in disease regulation、RNA Research and Splicing

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 h...