Molecular Pathogenesis of the Coronin Family: CORO2A Facilitates Migration and Invasion Abilities in Oral Squamous Cell Carcinoma

International Journal of Molecular Sciences

Shunichi Asai¹  Naohiko Seki¹  Atsushi Kasamatsu²  Katsuhiro Uzawa²  Kenta Tsuneizumi²  Sachi Oshima²  Ikuko Kase-Kato²  Chikashi Minemura²  Ayaka Koma²  Toyoyuki Hanazawa³ 

[1] Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;Department of Otorhinolaryngology/Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;

关键词: oral squamous cell carcinoma;    coronin;    CORO2A;    microRNA;    miR-125b-5p;    miR-140-5p;   

DOI  :  10.3390/ijms222312684

来源: DOAJ

【 摘 要 】

In humans, the coronin family is composed of seven proteins containing WD-repeat domains that regulate actin-based cellular processes. Some members of the coronin family are closely associated with cancer cell migration and invasion. The Cancer Genome Atlas (TCGA) analysis revealed that CORO1C, CORO2A, and CORO7 were significantly upregulated in oral squamous cell carcinoma (OSCC) tissues (p < 0.05). Moreover, the high expression of CORO2A was significantly predictive of the 5-year survival rate of patients with OSCC (p = 0.0203). Overexpression of CORO2A was detected in OSCC clinical specimens by immunostaining. siRNA-mediated knockdown of CORO2A suppressed cancer cell migration and invasion abilities. Furthermore, we investigated the involvement of microRNAs (miRNAs) in the molecular mechanism underlying CORO2A overexpression in OSCC cells. TCGA analysis confirmed that tumor-suppressive miR-125b-5p and miR-140-5p were significantly downregulated in OSCC tissues. Notably, these miRNAs bound directly to the 3′-UTR of CORO2A and controlled CORO2A expression in OSCC cells. In summary, we found that aberrant expression of CORO2A facilitates the malignant transformation of OSCC cells, and that downregulation of tumor-suppressive miRNAs is involved in CORO2A overexpression. Elucidation of the interaction between genes and miRNAs will help reveal the molecular pathogenesis of OSCC.

【 授权许可】

Unknown