MiR-769-5p inhibits cancer progression in oral squamous cell carcinoma by directly targeting JAK1/STAT3 pathway.

Abstract

Oral squamous cell carcinoma (OSCC) is the most common human malignancy worldwide with a high mortality rate. MiR-769-5p has been reported to be downregulated in tissues and blood of OSCC patients. However, the exact roles and pathogenesis of miR-769-5p involved in OSCC remain unclear. The expressions of miR-769-5p and Janus kinase (JAK1) in OSCC tissues and cells were assessed by RT-qPCR and western blot assay. Expressions of apoptotic-related (Bcl-2, Bax, and cleaved-caspase 3) and EMT-associated proteins (MMP9, E-cadherin, N-cadherin, and Vimentin) were detected by western blot assay. The effect of miR-769-5p and JAK1 on proliferation, migration, invasion, and apoptosis was evaluated by CCK-8, transwell, and flow cytometry assays, respectively. The binding interaction of miR-769-5p and JAK1 were predicted by TargetScan and demonstrated by dual-luciferase reporter assays. The volume and weight of the tumor were measured in the subcutaneous transplantation experiment. MiR-769-5p was downregulated, and JAK1 was upregulated in OSCC tissues and cells. MiR-769-5p restrained Bcl-2, MMP9, N-cadherin, and Vimentin protein level and accelerated Bax, cleaved-caspase 3 and E-cadherin protein level, while JAK1 partly overturned these effects. Also, miR-769-5p suppressed proliferation, migration, invasion, and increased apoptosis of OSCC, while the reintroduction of JAK1 abolished these effects. Moreover, JAK1 was verified to be the target of miR-769-5p. In addition, miR-769-5p inhibited the development of OSCC cells in vivo. These results indicate that miR-769-5p suppressed OSCC cell development via targeting the JAK1/STAT3 pathway, providing an underlying therapeutic method for OSCC.