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环状 RNA VAPA 通过 miR-132/HOXA7 轴促进口腔癌细胞的增殖、迁移和侵袭。

circVAPA promotes the proliferation, migration and invasion of oral cancer cells through the miR-132/HOXA7 axis.

机构信息

Department of Stomatology, the Wuhan Sixth Hospital, Wuhan, China.

Department of Stomatology, the First Affiliated Hospital of Jinan University, Jinan, China.

出版信息

J Int Med Res. 2021 Jun;49(6):3000605211013207. doi: 10.1177/03000605211013207.

DOI:10.1177/03000605211013207
PMID:34102907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8193665/
Abstract

OBJECTIVE

To study the relationship between the circular RNA vesicle-associated membrane protein-associated protein A (circVAPA) and the pathogenesis of oral squamous cell carcinoma.

METHODS

The expression of circVAPA was detected by RT-qPCR. loss-of-function experiments were performed in Cal-27 cells. The malignant phenotype of cells was evaluated by cell counting kit-8, clone formation and transwell assays. Luciferase reporter assays were used to assess the circVAPA/miR-132/homeobox A (HOXA) regulatory axis.

RESULTS

circVAPA expression was significantly increased in oral cancer tissues and cells. The overall survival and progression-free survival of patients with oral cancer who exhibited high circVAPA expression were significantly shorter compared with those with low expression. circVAPA expression was closely related to tumor size, TNM stage and distant metastasis. circVAPA knockdown reduced the proliferation, invasion and migration of Cal-27 cells. MiR-132 was identified as a target of circVAPA in Cal-27 cells. Cotransfection with si-circVAPA and miR-132 inhibitor reversed the inhibitory effect of circVAPA knockdown on cell malignant phenotypes. HOXA7 was further identified as a downstream target of miR-132.

CONCLUSION

circVAPA is highly expressed in oral cancer, and its abnormal expression might affect the proliferation, invasion and migration of oral cancer cells by modulating the miR-132/HOXA7 signaling axis.

摘要

目的

研究环状 RNA 囊泡相关膜蛋白相关蛋白 A(circVAPA)与口腔鳞状细胞癌发病机制的关系。

方法

采用 RT-qPCR 检测 circVAPA 的表达。在 Cal-27 细胞中进行功能丧失实验。通过细胞计数试剂盒-8、克隆形成和 Transwell 分析评估细胞的恶性表型。采用荧光素酶报告基因实验评估 circVAPA/miR-132/同源盒 A(HOXA)调节轴。

结果

circVAPA 在口腔癌组织和细胞中表达显著增加。circVAPA 高表达的口腔癌患者的总生存期和无进展生存期明显短于低表达的患者。circVAPA 的表达与肿瘤大小、TNM 分期和远处转移密切相关。circVAPA 敲低可降低 Cal-27 细胞的增殖、侵袭和迁移能力。miR-132 被鉴定为 Cal-27 细胞中 circVAPA 的靶标。si-circVAPA 和 miR-132 抑制剂的共转染逆转了 circVAPA 敲低对细胞恶性表型的抑制作用。HOXA7 进一步被鉴定为 miR-132 的下游靶标。

结论

circVAPA 在口腔癌中高表达,其异常表达可能通过调节 miR-132/HOXA7 信号通路影响口腔癌细胞的增殖、侵袭和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/8614b6421288/10.1177_03000605211013207-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/4bf80ef80657/10.1177_03000605211013207-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/3f1c73056214/10.1177_03000605211013207-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/d7d12f56a348/10.1177_03000605211013207-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/54b175b92b16/10.1177_03000605211013207-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/8614b6421288/10.1177_03000605211013207-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/4bf80ef80657/10.1177_03000605211013207-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/3f1c73056214/10.1177_03000605211013207-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/d7d12f56a348/10.1177_03000605211013207-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/54b175b92b16/10.1177_03000605211013207-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/268f/8193665/8614b6421288/10.1177_03000605211013207-fig5.jpg

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