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PMID: 32014687 Published · ppublish English Journal Article

Overexpression of circRNA_100290 promotes the progression of laryngeal squamous cell carcinoma through the miR-136-5p/RAP2C axis.

Wang Z, Huang C, Zhang A, Lu C, Liu L

Abstract

Circular RNAs (circRNAs) exert critical functions in tumorigenesis and tumor development, but whether and how circRNAs contribute to laryngeal squamous cell carcinoma (LSCC) is unclear. In this study, we explored the function and mechanisms of circRNA_100290 in LSCC. Tissue samples were obtained from 40 patients with LSCC. The expression of circRNA_100290 and other targets was measured through quantitative reverse transcription-polymerase chain reaction and western blot analysis. Cell proliferation, colony-forming ability, and apoptosis were tested using CCK-8 assay and EdU assay, colony formation assay, and flow cytometry, respectively. Cell migration and invasion were detected by Transwell assay. Moreover, the interactions between circRNA_100290, miR-136-5p, and RAP2C were analyzed by bioinformatics, and verified by dual-luciferase reporter assays. Here, we found that circRNA_100290 expression was significantly upregulated in LSCC tissues and cell lines compared with the normal controls. Expression of circRNA_100290 positively correlated with advanced TNM stage and lymph node metastasis in LSCC patients. In cell culture, upregulation of circRNA_100290 promoted LSCC cell proliferation, migration, and invasion, while it inhibited cell apoptosis; downregulating circRNA_100290 exerted the opposite effects. In vivo, circRNA_100290 overexpression dramatically promoted tumor growth. Mechanistically, circRNA_100290 may act as a sponge of miR-136-5p, and inhibiting miR-136-5p in LSCC cells indeed reversed the effects of circRNA_100290 downregulation. The RAS oncogene RAP2C was predicted to be a target of miR-136-5p, and downregulating RAP2C in LSCC cells partially reversed the oncogenic effects of circRNA_100290 overexpression or miR-136-5p decrease. Our findings suggest that circRNA_100290 promotes LSCC progression by targeting the miR-136-5p/RAP2C axis, which may lead to the identification of potential therapeutic targets.

Keywords
Laryngeal squamous cell carcinoma RAP2C circRNA_100290 miR-136-5p
MeSH Terms
Adult Aged Animals Apoptosis Carcinoma, Squamous Cell/genetics,pathology Cell Line, Tumor Cell Movement Disease Models, Animal Disease Progression Female Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Laryngeal Neoplasms/genetics,pathology Male Mice MicroRNAs/genetics Middle Aged Neoplasm Grading Neoplasm Staging Promoter Regions, Genetic RNA Interference RNA, Circular/genetics Xenograft Model Antitumor Assays ras Proteins/genetics
Chemicals
MIRN136 microRNA, human MicroRNAs RNA, Circular Rap2C protein, human ras Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wang Zhenxiao
Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China. Electronic address: zhenxiao_wang@ccmu.edu.cn.
Huang Chaoping
Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China. Electronic address: caogua2008@sina.com.
Zhang Aobo
Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China. Electronic address: geniusbo@163.com.
Lu Cheng
Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China. Electronic address: lucheng2@126.com.
Liu Liangfa
Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China. Electronic address: liuliangfa1@126.com.
Conflict of Interest

Declaration of Competing Interest The authors declare that there are no conflicts of interest.

Article Info
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Abbr.
Biomed Pharmacother
ISSN
1950-6007
Published
2020-05-00
Epub
2020-00-31
Pages
109874
Language
English
Region
France
NLM ID
8213295
Subset
IM
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