miR-488-3p sponged by circ-0000495 and mediated upregulation of TROP2 in head and neck squamous cell carcinoma development

Abstract

TROP2 (trophoblast cell surface antigen 2) overexpression has been reported in many human cancers. The correlation between TROP2 and tumor aggressiveness has implied it could be a prognostic indicator. However, the roles of TROP2 and their underlying mechanisms remain of great interest in head and neck squamous cell carcinoma (HNSCC) biology. In the current study, the prognostic significance of TROP2 in HNSCC archival samples was determined using immunohistochemistry. Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure the phenotypic effects of TROP2 knockdown, miR-488-3p re-expression, and circRNAs expression. Cell viability, migration/invasion as well as in vivo tumor formation assays were accessed. The interactions of miRNAs-TROP2 or circRNAs-miRNAs were determined by qRT-PCR, western blot analysis and luciferase assays. TROP2 was demonstrated overexpression in HNSCC patients and cancer cell lines. High expression of TROP2 was significantly associated with patient relapse. TROP2 promoted tumor cell proliferation, migration, invasion, and tumor growth, through AKT and MAPK pathways. Further investigation revealed that TROP2 is a direct target of miR-488-3p, while circ-0000495 bounds to miR-488-3p. Our study unraveled a novel mechanism by which down-regulation of miR-488-3p sponged by circ-0000495 releases its epigenetic silencing to TROP2. The increased TROP2 promotes tumor proliferation, therefore, providing evidence in support of targeting the circ-0000495/miR-488-3p/TROP2 axis in contributing to HNSCC therapy and preventing tumor metastasis.

The circ_0032822 Promotes the Proliferation of Head and Neck Squamous Cell Carcinoma Cells Through miR-141/EF3 Signaling Axis

“…Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of human malignancy and involves carcinoma of several anatomic sites, such as lip, oral cavity, pharynx (nasopharynx, oropharynx, hypopharynx), and larynx, with an annual incidence of~600,000 per year (12,13). Although the diagnosis and treatment have advanced in recent years, HNSCC still has a high incidence and mortality rate in developing countries (14,15).…”

Trop2: Jack of All Trades, Master of None

“…Epigenetic factors were identified as important modulators of Trop2 expression in cancers, too. Hao et al recently described circRNA—miR-488-3p—Trop2 regulatory loop that released Trop2 epigenetic silencing in head-and-neck squamous cell carcinoma cell lines [ 118 ]. Other miRNAs that target Trop2 were also identified in head-and-neck carcinoma [ 134 ] and urothelial bladder cancer [ 135 ].…”

The expression profile and clinical application value of hsa_circ_0016148 in head and neck squamous cell carcinoma

“…Wang et al 36 revealed that circRNA_103862 promotes the proliferation and invasion of laryngeal squamous cell carcinoma through targeting the miR‐493‐5p/GOLM1 axis, and it might serve as a prognostic indicator and anti‐cancer target for laryngeal squamous cell carcinoma. Hao et al 37 found that upregulated circ‐0000495 mediates overexpression of TROP2 by sponging miR‐488‐3p to promote tumor progression and is associated with patient survival in HNSCC. Here, we explored the potential biological function of hsa_circ_0016148 in HNSCC tumorigenesis through bioinformatics analysis by constructing a hsa_circ_0016148‐miRNA‐mRNA interaction network.…”