Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis

被引:113
|
作者
Wu, Yongyan [1 ,2 ,3 ,4 ,5 ]
Zhang, Yuliang [1 ,2 ]
Zheng, Xiwang [1 ,2 ]
Dai, Fengsheng [1 ,3 ]
Lu, Yan [6 ]
Dai, Li [1 ,3 ]
Niu, Min [1 ,2 ]
Guo, Huina [1 ,2 ]
Li, Wenqi [1 ,3 ]
Xue, Xuting [1 ,2 ]
Bo, Yunfeng [7 ]
Guo, Yujia [1 ,2 ]
Qin, Jiangbo [8 ]
Qin, Yixiao [1 ,3 ]
Liu, Hongliang [1 ,2 ,9 ]
Zhang, Yu [4 ,10 ]
Yang, Tao [5 ]
Li, Li [9 ]
Zhang, Linshi [11 ]
Hou, Rui [12 ,13 ]
Wen, Shuxin [14 ]
An, Changming [15 ]
Li, Huizheng [16 ]
Xu, Wei [17 ,18 ,19 ]
Gao, Wei [1 ,2 ,3 ,4 ,9 ]
机构
[1] Shanxi Med Univ, Shanxi Key Lab Otorhinolaryngol Head & Neck Canc, Taiyuan 030001, Shanxi, Peoples R China
[2] Shanxi Med Univ, Hosp 1, Shanxi Prov Clin Med Res Ctr Precis Med Head & Ne, Taiyuan 030001, Shanxi, Peoples R China
[3] Shanxi Med Univ, Hosp 1, Dept Otolaryngol Head & Neck Surg, Taiyuan 030001, Shanxi, Peoples R China
[4] Shanxi Med Univ, Minist Educ, Key Lab Cellular Physiol, Taiyuan 030001, Shanxi, Peoples R China
[5] Shanxi Med Univ, Dept Biochem & Mol Biol, Taiyuan 030001, Shanxi, Peoples R China
[6] Jinzhou Med Univ, Hosp 1, Dept Otolaryngol Head & Neck Surg, Jinzhou 121001, Liaoning, Peoples R China
[7] Shanxi Med Univ, Shanxi Canc Hosp, Dept Pathol, Taiyuan 030013, Shanxi, Peoples R China
[8] Changzhi Med Coll, Heping Hosp, Dept Otolaryngol Head & Neck Surg, Changzhi 046000, Shanxi, Peoples R China
[9] Shanxi Med Univ, Basic Med Sch, Dept Cell Biol & Genet, Taiyuan 030001, Shanxi, Peoples R China
[10] Shanxi Med Univ, Dept Physiol, Taiyuan 030001, Shanxi, Peoples R China
[11] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Hepatobiliary & Pancreat Surg, Hangzhou 310009, Zhejiang, Peoples R China
[12] Univ Western Australia, QEII Med Ctr, Harry Perkins Inst Med Res, POB 7214,6 Verdun St, Perth, WA, Australia
[13] Univ Western Australia, Ctr Med Res, POB 7214,6 Verdun St, Perth, WA, Australia
[14] Shenzhen Univ, Gen Hosp, Shenzhen 518055, Guangdong, Peoples R China
[15] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Dept Head & Neck Surg, Beijing 100021, Peoples R China
[16] Dalian Med Univ, Dalian Municipal Friendship Hosp, Dept Otolaryngol Head & Neck Surg, Dalian 116100, Liaoning, Peoples R China
[17] Shandong Univ, Shandong Prov ENT Hosp, Jinan 250022, Shandong, Peoples R China
[18] Shandong Prov Inst Otolaryngol, Jinan 250022, Shandong, Peoples R China
[19] Shandong Univ, Minist Hlth, Key Lab Otolaryngol, Jinan 250022, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
circCORO1C; Let-7c-5p; PBX3; Laryngeal squamous cell carcinoma; Epithelial-mesenchymal transition; Metastasis; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER PROGRESSION; MIGRATION; CIRCRNA; PBX3; INVASION; GROWTH; GENE;
D O I
10.1186/s12943-020-01215-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown. Methods RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C, let-7c-5p, and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry. Results circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3, which promoted the epithelial-mesenchymal transition and finally facilitated the malignant progression of LSCC. Conclusions circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.
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页数:18
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