Circular RNA hsa_circ_001895 serves as a sponge of microRNA-296-5p to promote clear cell renal cell carcinoma progression by regulating SOX12

被引:66
|
作者
Chen, Zhuangfei [1 ]
Xiao, Kanghua [2 ,3 ]
Chen, Shijun [1 ]
Huang, Zehai [1 ]
Ye, Yunlin [2 ,3 ]
Chen, Tong [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Urol, Guangzhou, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Ctr Canc, Dept Urol, Guangzhou, Guangdong, Peoples R China
[3] State Key Lab Oncol Southern China, Guangzhou, Guangdong, Peoples R China
关键词
clear cell renal cell carcinoma; hsa_circ_001895; miR-296-5p; progression; SOX12; HEPATOCELLULAR-CARCINOMA; MESENCHYMAL TRANSITION; CANCER; METASTASIS; ACTIVATION; GUIDELINES; GROWTH;
D O I
10.1111/cas.14261
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
There is an urgent need to find novel potential therapeutic targets for the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC) due to its highly invasive ability as a common urological malignant tumor. Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression. We first used qRT-PCR analysis to find dysregulated circRNAs in ccRCC. A novel circRNA, hsa_circ_001895, was upregulated in ccRCC specimens and associated with metastatic properties of ccRCC. However, the tumorigenic mechanism of hsa_circ_001895 on ccRCC is yet to be found. We first indicated that hsa_circ_001895 predicted a poor prognosis in ccRCC patients. Additionally, overexpression of hsa_circ_001895 not only promoted cell proliferation, invasion and migration of ccRCC, but also inhibited cell apoptosis, whereas hsa_circ_001895 knockdown reversed the effect on ccRCC progression. In vivo s.c. xenotransplanted tumor model also showed that silencing hsa_circ_001895 could suppress in vivo ccRCC growth. Mechanistically, hsa_circ_001895 directly binds with microRNA (miR)-296-5p and inhibits its expression. Moreover, sex determining region Y (SRY)-box 12 (SOX12) was identified as a target of miR-296-5p, the expression of which was suppressed by miR-296-5p. Notably, the inhibitory effect of hsa_circ_001895 on ccRCC progression was reversed by miR-296-5p inhibitor. In general, our findings indicated that hsa_circ_001895 may sponge miR-296-5p and promote SOX12 expression, which is the underlying mechanism of hsa_circ_001895-induced ccRCC progression.
引用
收藏
页码:713 / 726
页数:14
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