title: MiR-139 targets CXCR4 and inhibits the proliferation and metastasis of laryngeal squamous carcinoma cells.
abstract: Our previous studies have showed that chemokine receptor 4 (CXCR4) was over-expressed in laryngeal squamous cell carcinoma (LSCC). However, the mechanism underlying aberrant CXCR4 expression remains unclear. To investigate the roles played by miRNAs in CXCR4 over-expression in LSCC, putative miR-139 was predicted through computational algorithms, including TargetScan, PicTar and miRBase, and luciferase reporter assay was explored to confirm that whether CXCR4 was directly regulated by miR-139. Then, quantitative real-time PCR, immunohistochemistry and in situ hybridization methods were employed to detect the expression of miR-139 and CXCR4 in primary LSCC tissues, normal adjacent mucosal tissues and metastatic lesions derived from 40 LSCC patients in the Second Hospital, Xi'An JiaoTong University. Finally, gain- and loss-of-function assays were adopted to explore the effects of miR-139 and CXCR4 on proliferation, invasion and metastasis of the human LSCC cell line Hep-2 in vitro and in vivo. Our results showed that miR-139 dampened CXCR4 expression, and CXCR4 was directly targeted by miR-139. Additionally, the expression of miR-139 was reduced in alignment with the progression of primary to metastatic LSCC. Moreover, an inverse correlation was observed between miR-139 and CXCR4 protein levels in LSCC specimens. Functional analyses demonstrated that ectopic expression of miR-139 inhibited cell proliferation, migration and metastasis of Hep-2 cells in vitro and in vivo. Similar to the observations seen in restoring miR-139 expression, dampening of CXCR4 expression inhibited cell growth, migration and invasion, whereas miR-139 over-expression reversed the pro-metastatic effect of CXCR4. Taken together, we conclude that miR-139 targets CXCR4 and inhibits proliferation and metastasis of LSCC.
authors: Department of Otolaryngology-Head and Neck Surgery, The Second Hospital, Xi'an Jiao Tong University, Xi Wu Road #157, Xi'an, 710004, Shan'Xi Province, China.
authors: Hua-Nan
authors: HN
authors: Luo
authors: Zheng-Hui
authors: ZH
authors: Wang
authors: Ying
authors: Y
authors: Sheng
authors: Qing
authors: Q
authors: Zhang
authors: Jing
authors: J
authors: Yan
authors: Jin
authors: J
authors: Hou
authors: Kang
authors: K
authors: Zhu
authors: Ying
authors: Y
authors: Cheng
authors: Ying-Long
authors: YL
authors: Xu
authors: Xiang-Hong
authors: XH
authors: Zhang
authors: Min
authors: M
authors: Xu
authors: Xiao-Yong
authors: XY
authors: Ren
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: C527276:CXCR4 protein, human; C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D019718:Receptors, CXCR4