Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer and is associated with high recurrence, poor treatment, and low survival rates. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that regulates the response to hypoxia, a major factor in the tumor microenvironment that affects tumor development and progression in various cancer types. However, microRNA (miRNA) sequence analysis revealed that only a few miRNAs targeting HIF-1α had been discovered. In the present study, we investigated HIF-1α expression in OSCC and the effect of HIF-1α-targeting miRNAs on the progression and metastatic potential of OSCC. We analyzed public databases to explore which miRNAs target HIF-1α expression. In addition, the expression of proteins involved in the cell cycle, proliferation, and apoptosis in HSC-2 cells was analyzed after miRNA-126 mimic treatment. Furthermore, to investigate the effect of miRNA-126 on the proliferation and invasion ability of OSCC cells, 5-ethynyl-2′-deoxyuridine and Transwell assays were performed. The activities of MMP-2 and MMP-9 were evaluated via gelatin zymography. Our results showed that miRNA-126, which targets HIF-1α, enhances OSCC cell proliferation by regulating the cell cycle and reinforces the cell mobility of OSCC via HIF-1α expression. These findings suggest that miRNA-126 may be a novel marker for OSCC treatment and the development of new tools for patients with OSCC.

Abstract
Ⅰ. INTRODUCTION
Ⅱ. MATERIALS AND METHODS
    1. OSCC cell lines and cell culture
    2. RNA isolation and quantitative real-timepolymerase chain reaction (qRT-PCR)
    3. Western blotting
    4. 5-Ethynyl-2′-deoxyuridine (EdU) assay
    5. Migration assay using Transwell inserts
    6. Gelatin zymography
    7. Statistical analysis
Ⅲ. RESULTS
    1. miRNA-126 targets HIF-1α and upregulatesthe expression of HIF-1α in OSCC cells
    2. miRNA-126 regulates the cell cycle in OSCCcells
    3. miRNA-126 regulates the apoptosis and cellproliferation rates of OSCC cells
    4. miRNA-126 regulates cell proliferation OSCC cells
    5. miRNA-126 regulates the migration ability ofOSCC cells
Ⅳ. DISCUSSION
ACKNOWLEDGMENTS
REFERENCES

• 박수연(강릉원주대학교 치과대학 병리학교실) | Suyeon Park (Department of Pathology, College of Dentistry, Gangneung-Wonju National University)
• 오지현(강릉원주대학교 치과대학 구강악안면외과학 교실) | Ji-Hyeon Oh (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University)
• 이상신(강릉원주대학교 치과대학 병리학교실) | Sang Shin Lee (Department of Pathology, College of Dentistry, Gangneung-Wonju National University)
• 최종호(강릉원주대학교 치과대학 병리학교실) | Jongho Choi (Department of Pathology, College of Dentistry, Gangneung-Wonju National University) Corresponding Author