miR-424-5p Promotes Proliferation, Migration and Invasion of Laryngeal Squamous Cell Carcinoma

Abstract

Yujun Li,1–4,* Jie Liu,5,* Wanglai Hu,6,* Yuliang Zhang,1–4,* Jiangwei Sang,1–4 Huizheng Li,7 Teng Ma,8 Yunfeng Bo,9 Tao Bai,10 Huina Guo,1–4 Yan Lu,11 Xuting Xue,1–4 Min Niu,1–4 Shanshan Ge,12 Shuxin Wen,1–4 Binquan Wang,1–4 Wei Gao,1–4 Yongyan Wu1–4 1Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, People’s Republic of China; 2Department of Otolaryngology Head & Neck Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, People’s Republic of China; 3Otolaryngology Head & Neck Surgery Research Institute, Shanxi Medical University, Taiyuan, Shanxi 030001, People’s Republic of China; 4The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Shanxi Province, Taiyuan 030001, Shanxi, People’s Republic of China; 5Department of Head and Neck Surgical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 6School of Basic Medical Science, Anhui Medical University, Hefei, Anhui 230027, People’s Republic of China; 7Department of Otolaryngology Head & Neck Surgery, Dalian Municipal Friendship Hospital, Dalian, Liaoning 116001, People’s Republic of China; 8Department of Cellular and Molecular Biology, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing 101149, People’s Republic of China; 9Department of Pathology, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan, Shanxi 030000, People’s Republic of China; 10Department of Pathology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, People’s Republic of China; 11Department of Otolaryngology Head & Neck Surgery, The First Hospital, Jinzhou Medical University, Jinzhou 121001, Liaoning, People’s Republic of China; 12Health Management Center, the First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongyan Wu; Wei GaoShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, The First Hospital of Shanxi Medical University, No. 85, South Jiefang Road, Taiyuan, Shanxi 030001, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]; [email protected]: Recent studies revealed that miR-424-5p regulates the malignant behavior of multiple cancer types. However, the expression and function of miR-424-5p in laryngeal squamous cell carcinoma (LSCC) is unclear.Purpose: This study aimed to evaluate the association of miR-424-5p level with clinical features of LSCC and investigate the effect and potential mechanism of miR-424-5p on LSCC progression.Methods: The expression of miR-424-5p in LSCC and paired adjacent normal margin (ANM) tissues from 106 patients with LSCC were analyzed by quantitative PCR (qPCR), and clinical significance was analyzed. Target genes of miR-424-5p were predicted, followed by functional annotation. The functional role of miR-424-5p in LSCC was investigated by molecular and cellular experiments with LSCC cell lines, with flow cytometry used for cell cycle analysis. In addition, miR-424-5p regulation of the predicted target gene cell adhesion molecule 1 (CADM1) was validated by qPCR, Western blot analysis and luciferase reporter assay.Results: miR-424-5p was upregulated in LSCC versus ANM tissues. High miR-424-5p level was significantly associated with poor differentiation, advanced tumor stage and cervical lymph node metastasis. Bioinformatics analysis showed that miR-424-5p target genes are mainly enriched in biological processes of the cell cycle, cell division, and negative regulation of cell migration, and were involved in multiple cancer-related pathways. Overexpression of miR-424-5p promoted proliferation, migration, invasion, and adhesion of LSCC cells and affected the cell cycle progression. Additionally, CADM1 was a direct target of miR-424-5p in LSCC cells.Conclusion: miR-424-5p functions as an oncogene to promote the aggressive progression of LSCC, and CADM1 is a direct downstream target of miR-424-5p in LSCC cells. miR-424-5p may be a potential therapeutic target in LSCC.Keywords: laryngeal squamous cell carcinoma, miR-424-5p, proliferation, migration and invasion, oncogenic miRNA

Keywords

• laryngeal squamous cell carcinoma
• mir-424-5p
• proliferation
• migration and invasion
• oncogenic mirna