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

Molecular Pathogenesis of the Coronin Family: CORO2A Facilitates Migration and Invasion Abilities in Oral Squamous Cell Carcinoma.
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DOI:
10.3390/ijms222312684
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发表时间:
2021-11-24
影响因子:
5.6
通讯作者:
Seki N
Seki N
中科院分区:
生物学2区
文献类型:
--
作者:
Kase-Kato I;Asai S;Minemura C;Tsuneizumi K;Oshima S;Koma A;Kasamatsu A;Hanazawa T;Uzawa K;Seki N

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在人类中,柯拉宁家族由七种含有WD重复结构域的蛋白质组成,这些结构域调节基于肌动蛋白的细胞过程。冠状病毒家族的一些成员与癌细胞的迁移和侵袭密切相关。肿瘤基因组图谱(TCGA)分析显示CORO1C、CORO2A和CORO7在口腔鳞状细胞癌(OSCC)组织中显著上调(p<0.05)。此外,CORO2A的高表达可显著预测口腔鳞癌患者的5年生存率(p=0.0203)。免疫组织化学染色显示CORO2A在口腔鳞癌临床标本中呈高表达。SiRNA介导的CORO2A基因敲除抑制了癌细胞的迁移和侵袭能力。此外,我们还研究了microRNAs(MiRNAs)在口腔鳞状细胞癌CORO2A过表达的分子机制中的作用。TCGA分析证实抑癌基因miR-125b-5p和miR-140-5p在口腔鳞癌组织中表达显著下调。值得注意的是,这些miRNAs直接与CORO2A的3‘-UTR结合,并控制CORO2A在口腔鳞癌细胞中的表达。综上所述,我们发现CORO2A的异常表达促进了口腔鳞癌细胞的恶性转化,而抑制肿瘤的miRNAs的下调参与了CORO2A的过度表达。阐明基因和miRNAs之间的相互作用将有助于揭示口腔鳞癌的分子发病机制。
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.
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