Circular RNA hsa_circ_001895 serves as a sponge of microRNA-296-5p to promote clear cell renal cell carcinoma progression by regulating SOX12
Circular RNA hsa_circ_001895 serves as a sponge of microRNA-296-5p to promote clear cell renal cell carcinoma progression by regulating SOX12
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DOI：
10.1111/cas.14261
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发表时间：
2019-12-30
期刊：
影响因子：
5.7
通讯作者：
Chen, Tong
中科院分区：
文献类型：
--
作者：
Chen, Zhuangfei;Xiao, Kanghua;Chen, Tong
肾透明细胞癌（clear cell renal cell carcinoma，ccRCC）是泌尿系统常见的恶性肿瘤，具有高度侵袭性，迫切需要寻找新的治疗靶点。环状RNA（circRNA）已被指示为各种类型的肿瘤进展中的潜在关键介质。我们首先使用qRT-PCR分析来发现ccRCC中失调的circRNA。一种新的circRNA hsa_circ_001895在ccRCC标本中上调，并与ccRCC的转移特性相关。然而，hsa_circ_001895对ccRCC的致瘤机制尚未被发现。我们首次指出，hsa_circ_001895预测ccRCC患者的预后不良。此外，hsa_circ_001895的过表达不仅促进了ccRCC细胞的增殖、侵袭和迁移，而且抑制了细胞凋亡，而hsa_circ_001895的敲低逆转了对ccRCC进展的影响。体内皮下注射异种移植肿瘤模型也显示沉默hsa_circ_001895可抑制体内ccRCC生长。在机制上，hsa_circ_001895直接与microRNA（miR）-296-5p结合并抑制其表达。此外，性别决定区Y（SRY）-盒12（SOX 12）被鉴定为miR-296- 5 p的靶点，其表达被miR-296- 5 p抑制。值得注意的是，hsa_circ_001895对ccRCC进展的抑制作用被miR-296- 5 p抑制剂逆转。总之，我们的研究结果表明，hsa_circ_001895可能海绵miR-296- 5 p并促进SOX 12表达，这是hsa_circ_001895诱导ccRCC进展的潜在机制。
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.