A circular RNA derived from MMP9 facilitates oral squamous cell carcinoma metastasis through regulation of MMP9 mRNA stability

Cell Transplantation

Original Articles

Yongbo Gao¹  Xinlan Hu¹  Bing Xia¹  Tao Hong¹  Xin He¹ 

[1] Department of Stomatology, Hangzhou Red Cross Hospital, Hangzhou, China;

关键词: Circular RNA;    OSCC;    mRNA stability;    metastasis;    biomarker;   

DOI  :  10.1177/0963689719875409

 received in 2019-07-22, accepted in 2019-08-19,  发布年份 2019

来源: Sage Journals

【 摘 要 】

Emerging evidence demonstrates that dysregulation of circular RNA is linked to tumorigenesis and aggressive progression. However, its role in oral squamous cell carcinoma remains largely uncharacterized. In this study, we identified a novel metastasis-associated circular RNA, circular matrix metalloproteinase 9 (hsa_circ_0001162, a circular RNA derived from matrix metalloproteinase 9), which was remarkably upregulated in oral squamous cell carcinoma and positively correlated with matrix metalloproteinase 9 expression. Patients with high circular matrix metalloproteinase 9 expression were prone to lymph node metastasis and an advanced TNM stage. Importantly, circular matrix metalloproteinase 9 was identified as an efficacious diagnostic and prognostic biomarker for oral squamous cell carcinoma patients. Functional experiments showed that depletion of circular matrix metalloproteinase 9 weakened the migratory and invasive capabilities of oral squamous cell carcinoma cells in vitro as well as inhibited lung metastasis in vivo. Regarding the mechanism, circular matrix metalloproteinase 9 could simultaneously interact with AUF1 and miR-149 to block the inhibitory effect of AUF1 and miR-149 on matrix metalloproteinase 9 3′-untranslated region, resulting in enhanced matrix metalloproteinase 9 messenger RNA stability, thereby facilitating oral squamous cell carcinoma metastasis. Collectively, our data indicate that circular matrix metalloproteinase 9 acts as a metastasis-promoting gene in oral squamous cell carcinoma through regulating the messenger RNA stability of its parental gene. Therapeutic targeting of circular matrix metalloproteinase 9 may be a promising treatment intervention for metastatic oral squamous cell carcinoma patients.

【 授权许可】

CC BY-NC   
© The Author(s) 2019

【 图 表 】

Figure 9.