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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.
Insights
MicroRNA-769-5p (miR-769-5p) suppresses oral squamous cell carcinoma (OSCC) development by targeting Janus kinase 1 (JAK1). This finding offers a potential new therapeutic strategy for OSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent and deadly cancer.
- The role of microRNA-769-5p (miR-769-5p) in OSCC pathogenesis is not fully understood.
- Previous studies suggest miR-769-5p is downregulated in OSCC.
Purpose of the Study:
- To investigate the role and mechanism of miR-769-5p in OSCC.
- To determine if miR-769-5p targets Janus kinase 1 (JAK1) in OSCC.
- To evaluate the therapeutic potential of miR-769-5p in OSCC.
Main Methods:
- Quantitative real-time PCR and Western blot to assess miR-769-5p and JAK1 expression.
- Cellular assays (CCK-8, Transwell, flow cytometry) to evaluate proliferation, migration, invasion, and apoptosis.
- Dual-luciferase reporter assay to confirm the interaction between miR-769-5p and JAK1.
- In vivo subcutaneous transplantation experiments in mice.
Main Results:
- MiR-769-5p was significantly downregulated, while JAK1 was upregulated in OSCC tissues and cells.
- MiR-769-5p inhibited OSCC cell proliferation, migration, and invasion, while promoting apoptosis.
- JAK1 was identified as a direct target of miR-769-5p, and its reintroduction reversed the effects of miR-769-5p.
- MiR-769-5p suppressed OSCC tumor growth in vivo.
Conclusions:
- MiR-769-5p acts as a tumor suppressor in OSCC by targeting JAK1.
- The miR-769-5p/JAK1 axis influences apoptosis and epithelial-mesenchymal transition (EMT)-related proteins.
- Targeting the JAK1/STAT3 pathway via miR-769-5p represents a promising therapeutic strategy for OSCC.
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