title: miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma.
abstract: 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.
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.|Department of Head and Neck Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Lie-Hao
authors.initials: LH
authors.lastname: Jiang
authors.affiliation: Department of Head and Neck Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Ge
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.|Department of Head and Neck Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Xiu-Xiu
authors.initials: XX
authors.lastname: Hou
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.|Department of Head and Neck Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.|Department of Head and Neck Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Hu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.|Department of Head and Neck Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Lu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.
authors.forename: Lian-Lian
authors.initials: LL
authors.lastname: Hong
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou 310022, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ling
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism* / Q000401:mortality; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000401:mortality
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human