miR-1207-5p suppresses laryngeal squamous cell carcinoma progression by downregulating SKA3 and inhibiting epithelial-mesenchymal transition

被引:10
|
作者
Wu, Yongyan [1 ,2 ,3 ,4 ]
Dai, Fengsheng [2 ]
Zhang, Yuliang [2 ]
Zheng, Xiwang [1 ,2 ]
Li, Li [5 ]
Zhang, Yu [3 ]
Cao, Jimin [3 ]
Gao, Wei [1 ,2 ,3 ,5 ]
机构
[1] Shenzhen Univ, Gen Hosp, Clin Med Acad, Shenzhen 518055, Guangdong, Peoples R China
[2] Shanxi Med Univ, Shanxi Prov Clin Med Res Ctr Precis Med Head & Ne, Shanxi Key Lab Otorhinolaryngol Head & Neck Canc, Hosp 1, Taiyuan 030001, Shanxi, Peoples R China
[3] Shanxi Med Univ, Key Lab Cellular Physiol, Minist Educ, Taiyuan 030001, Shanxi, Peoples R China
[4] Shanxi Med Univ, Dept Biochem & Mol Biol, Taiyuan 030001, Shanxi, Peoples R China
[5] Shanxi Med Univ, Dept Cell Biol & Genet, Basic Med Sch, Taiyuan 030001, Shanxi, Peoples R China
来源
MOLECULAR THERAPY-ONCOLYTICS | 2021年 / 22卷
基金
中国国家自然科学基金;
关键词
MESSENGER-RNA; CANCER CELLS; PROMOTES; METASTASIS; CHEMORESISTANCE; PROLIFERATION; GROWTH; MIRNA;
D O I
10.1016/j.omto.2021.08.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Laryngeal squamous cell carcinoma (LSCC) is the second most common head and neck cancer. Previously, we discovered that miR-1207-5p was downregulated in LSCC. In this study, the clinical significance, function, and mechanism of miR-12075p in LSCC were investigated. Downregulation of miR-12075p was found to be strongly linked to the malignant progression of LSCC. Functional studies revealed that miR-1207-5p upregulation suppressed LSCC cell proliferation, invasion, migration, and xenograft tumor growth. Bioinformatics analysis revealed that miR-1207-5p target genes were involved in cell cycle regulation, proliferation, adhesion, and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Mechanistic studies revealed that miR-1207-5p interacts directly with the 30 untranslated region of spindle and kinetochore associated complex subunit 3 (SKA3) and downregulates SKA3 expression. Furthermore, SKA3 was found to be overexpressed in LSCC, and its high expression was associated with tumor progression and a poor prognosis. Rescue experiments demonstrated that miR-12075p inhibited the malignant phenotypes of LSCC via SKA3. Furthermore, miR-1207-5p upregulation or knockdown of SKA3 inhibited the epithelial-mesenchymal transition (EMT). Collectively, miR-1207-5p inhibited LSCC malignant progression by downregulating SKA3 and preventing EMT. These findings provide new insights into the mechanism of LSCC progression, as well as new potential biomarkers and therapeutic targets for LSCC diagnosis and treatment.
引用
收藏
页码:152 / 165
页数:14
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