Circ-AFAP1 promote clear cell renal cell carcinoma growth and angiogenesis by the Circ-AFAP1/miR-374b-3p/VEGFA signaling axis.
Circ-AFAP1 promote clear cell renal cell carcinoma growth and angiogenesis by the Circ-AFAP1/miR-374b-3p/VEGFA signaling axis.
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DOI：
10.1038/s41420-022-00865-1
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发表时间：
2022-02-16
影响因子：
7
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Ou Y;Dai X;Chen X;Chen Y;Wu S;Zhou Q;Yang C;Jiang H
肾透明细胞癌（Clear cell renal cell carcinoma，ccRCC）是泌尿生殖系统最常见的恶性肿瘤之一。环状RNA（circRNA）作为一种新兴的内源性RNA，已被证明在肾透明细胞癌（ccRCC）的进展中发挥着至关重要的作用。在这项研究中，我们通过高测序获得了在ccRCC中上调的circAFAP 1，并在几种肾癌细胞系中通过qRT-PCR进行了验证。原位杂交（ISH）分析和Kaplan-Meier曲线显示，circAFAP 1水平较高与总生存期较短相关。此外，CCK 8、集落形成和EdU实验显示circAFAP 1促进ccRCC生长，而管形成显示circAFAP 1有助于ccRCC血管生成。我们通过生物信息学分析预测了下游miR-374 b-3 p和VEGFA，并通过qRT-PCR、RNA pull-down、RIP和双荧光素酶进一步验证。下调miR-374 b-3 p或过表达VEGFA可恢复circAFAP 1沉默后的细胞增殖和血管形成。与体外结果一致，沉默circAFAP 1抑制体内ccRCC生长。结论：circAFAP 1/miR-374 b-3 p/VEGFA轴在ccRCC的发生发展中起重要作用，可能成为新的生物学标志物和治疗靶点。
Clear cell renal cell carcinoma (ccRCC) is one of the most common urogenital tumors with high mortality. Circular RNA (circRNA), as an emerging endogenous RNA, has been proved to play a crucial role in the clear cell renal cell carcinoma (ccRCC) progression. In this study, we obtained circAFAP1 upregulated in ccRCC by high-sequencing and verified by qRT-PCR in several renal cancer cell lines. In situ hybridization (ISH) assays and Kaplan–Meier plot showed a higher level of circAFAP1 was linked to shorter overall survival. Moreover, CCK8, colony formation, and EdU experiments showed circAFAP1 promoted ccRCC growth while tube formation displayed circAFAP1 contributed to ccRCC angiogenesis. We predicted the downstream miR-374b-3p and VEGFA by bioinformatic analysis and validated further by qRT-PCR, RNA pull-down, RIP, and dual-luciferase. Downregulation miR-374b-3p or overexpression VEGFA could restore proliferation, vascular formation after circAFAP1 silencing. Consistently with the results in vitro, silencing circAFAP1 suppressed ccRCC growth in vivo. In conclusion, the circAFAP1/miR-374b-3p/VEGFA axis played a critical role in the progression and development of ccRCC which might be novel biological marks and therapeutical targets.
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作者：
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DOI：
10.1016/j.omtn.2021.01.009
发表时间：
2021-03-05
期刊：
Molecular therapy. Nucleic acids
影响因子：
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作者：
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