OncoTargets and Therapy (Feb 2020)
miR-873-5p Inhibits Cell Migration and Invasion of Papillary Thyroid Cancer via Regulation of CXCL16
Abstract
Zhenglin Wang,* Wei Liu,* Cong Wang, Zhilong Ai Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhilong AiDepartment of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaEmail [email protected]: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer with an increasing morbidity. MicroRNAs (miRNAs) play the pivotal roles in PTC occurrence and development. The aim of this study was to investigate the biological functions of miR-873-5p and its underlying molecular mechanisms in PTC.Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect miR-873-5p expressions in PTC tissues and cell lines. The target gene of miR-873-5p was predicted by TargetScan and confirmed by dual-luciferase reporter assay. Furthermore, cell proliferation, migration and invasion were assessed by CCK-8, wound healing assay and transwell assay, respectively. Additionally, the expressions of CXCL16, MMP1, MMP9 and MMP13 were measured by RT-qPCR and Western blot methods, and p65, Rel-B and their phosphorylation levels were examined by Western blot.Results: We found that miR-873-5p expression was downregulated in PTC tissues and cell lines. Moreover, CXCL16 was identified as a target of miR-873-5p, and its expression was upregulated in PTC tissues and cells at both mRNA and protein levels. Functionally, overexpression of miR-873-5p inhibited PTC cell proliferation, migration and invasion, while co-transfection of CXCL16 overexpression plasmid reversed the anti-tumor behaviors induced by miR-873-5p. In addition, miR-873-5p overexpression suppressed the phosphorylation of p65 and Rel-B, and decreased the mRNA and protein expression of MMP1, MMP9 and MMP13, while overexpression of CXCL16 partially abrogated the effects of miR-873-5p.Conclusion: MiR-873-5p functions as a tumor suppressor in PTC by inhibiting the proliferation, migration and invasion of the PTC cells via targeting CXCL16. These findings might provide a potential novel target for the therapy of PTC.Keywords: papillary thyroid cancer, miR-873-5p, CXCL16, migration, invasion, proliferation
