[Frontiers in Bioscience, Landmark, 25, 1729-1742, June 1, 2020]

Progression of squamous cell carcinoma is regulated by miR-139-5p/CXCR4

Qian Jiang1, Yiting Cao2, Yating Qiu1, Chenlin Li1, Liu Liu3, Guangzhou Xu1

1Department of Oral Surgery, Shanghai Ninth People's Hospital affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China, 2Department of Pediatric Dentistry, Shanghai Ninth People's Hospital affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China, 3Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
    3.1. Materials and methods
    3.2. Cell culture
    3.3. Transient transfection
    3.4. MTT assay
    3.5. Transwell mobility assay
    3.6. Western blotting
    3.7. Quantitative real-time PCR (qRT-PCR)
    3.8. RNA immunoprecipitation (RIP) assay
    3.9. Dual-luciferase reporter assay
    3.10. Xenograft assay
    3.11. Statistical analysis
4. Results
    4.1. Low miR-139-5p expression signifies poor survival in OSCC
    4.2. Upregulation of miR-139-5p inhibits cell proliferation and mobility
    4.3. miR-139-5p targets CXCR4 and its downstream targets
    4.4. miR-139-5p suppresses the related-proteins of the proliferation and mobility by regulating CXCR4 in OSCC
    4.5. miR-139-5p/CXCR4 axis regulates proliferation and mobility of OSCC
    4.6. miR-139-5p restricts tumor growth in vivo
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

miR-139-5p has a tumor suppressor effect in some cancers and negatively regulates CXCR4. To this end, we examined the expression and mechanism of of action of miR-139-5p and CXCR4 in oral squamous cell carcinoma (OSCC). miRNA-139-5p was down-regulated whereas CXCR4 was increased in tissues and cells of OSCC. Moreover, low expression of miR-139-5p was associated with a low survival. Overexpression of miR-139-5p in OSCC inhibited in vitro and in vivo cell proliferation and in vitro mobility of OSCC and inhibited the expression of WNT responsive c-myc, cyclinD1, and Bcl-2, and such effects were all reversible by an inhibitor of miR-139-5p or over-expression of CXCR4. The inverse relation between expression of miR-139-5p and CXCR4 might be related to the fact that miR-139-5p negatively regulates CXCR4 expression by virtue of direct binding. These findings underscore the importance of miR-139-5p and CXCR4 in regulation of OSCC.

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Abbreviations: Oral Squamous Cell Carcinoma (OSCC); RNA Immunoprecipitation (RIP); 3’ Untranslated Region (3’-UTR); Epithelial–Mesenchymal Transition (EMT)

Key Words: Oral, Squamous Cell Carcinoma, miR-139-5p, Wnt, Beta-Catenin Signaling, Proliferation, Invasion

Send correspondence to: Liu Liu, Department of Oral and Maxillofacial-Head and Neck Oncology,Shanghai Ninth People's Hospital affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai Key Laboratory of Stomatology, No.639, Zhizaoju Rd, Shanghai, P. R. China, Tel:86-21-23271699, Fax:86-21-63136856, E-mail: liuliucycstal@163.com