MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1.
MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1.
复制标题
MicroRNA-153-5p通过直接靶向AGO1促进肾细胞癌的增殖和转移
DOI：
10.1038/s41419-020-03306-y
复制
发表时间：
2021-01-04
影响因子：
9
通讯作者：
Fan Y
中科院分区：
文献类型：
--
作者：
Li Z;Zhao S;Zhu S;Fan Y
microRNA（miRNAs）已被证明影响癌症的生物学过程，并显示出作为预后生物标志物的巨大潜力。在这项研究中，我们使用生物信息学算法，基于转移、预后和与正常组织相比的差异表达三个维度，筛选了ccRCC中差异表达的miRNA。miR-153- 5 p被鉴定为促进ccRCC发生和进展的候选miRNA。在临床上，我们发现miR-153- 5 p显著上调，并与ccRCC中不利的临床特征相关。此外，miR-153- 5 p可作为独立的预后生物标志物。在功能上，miR-153- 5 p缺失通过磷脂酰肌醇3-激酶（PI 3 K）/Akt信号传导显著抑制ccRCC的增殖和转移。AGO 1是miR-153- 5 p的直接靶点。AGO 1与有利的临床特征相关，并在ccRCC中表现出独立的预后价值。此外，我们观察到AGO 1敲低显著促进肿瘤增殖和转移。AGO 1的下调部分消除了miR-153- 5 p敲低的致癌作用。此外，miR-153- 5 p与AGO 1组合在ccRCC中显示出更强的预后意义。总之，我们发现新鉴定的miR-153- 5 p/AGO 1轴通过PI 3 K/Akt信号传导负责肿瘤的发生和进展，因此可能为ccRCC患者提供有希望的治疗靶点和预后生物标志物。
MicroRNAs (miRNAs) have been demonstrated to affect the biological processes of cancers and showed great potential for prognostic biomarkers. In this study, we screened differentially expressed miRNAs in ccRCC based on three dimensions of metastasis, prognosis, and differential expression compared to normal tissue using bioinformatics algorithms. MiR-153-5p was identified as a candidate miRNA to promote ccRCC occurrence and progression. Clinically, we found that miR-153-5p was significantly upregulated and related to unfavorable clinical features in ccRCC. Besides, miR-153-5p served as an independent prognostic biomarker. Functionally, miR-153-5p depletion remarkably inhibited the proliferation and metastasis of ccRCC via the phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Furthermore, AGO1 was proved to be a direct target of miR-153-5p. AGO1 is associated with favorable clinical features and exhibited independent prognostic value in ccRCC. Besides, we observed that AGO1 knockdown significantly promoted tumor proliferation and metastasis. Downregulation of AGO1 partly abolished the oncogenic effects of miR-153-5p knockdown. Furthermore, miR-153-5p combined with AGO1 showed more robust prognostic significance in ccRCC. In conclusion, we found that the newly identified miR-153-5p/AGO1 axis was responsible for tumor occurrence and progression via PI3K/Akt signaling, which may therefore provide promising therapeutic targets and prognostic biomarkers for patients with ccRCC.
登录
查看更多内容
miR-153抑制IDO1表达并增强CAR T细胞免疫治疗
影响因子：
28.5
作者：
Huang Q;Xia J;Wang L;Wang X;Ma X;Deng Q;Lu Y;Kumar M;Zhou Z;Li L;Zeng Z;Young KH;Yi Q;Zhang M;Li Y
通讯作者：
Li Y
影响因子：
3.9
作者：
Krebs, Markus;Solimando, Antonio Giovanni;Kneitz, Burkhard
通讯作者：
Kneitz, Burkhard
影响因子：
3.8
作者：
Anaya, Jordan
通讯作者：
Anaya, Jordan
长非编码 RNA-MALAT1 通过 PI3K/Akt 信号通路介导青光眼大鼠视网膜神经节细胞凋亡
影响因子：
--
作者：
Li, Hai-Bo;You, Qi-Sheng;Ji, Dan
通讯作者：
Ji, Dan
败酱乙醇提取物通过 SIRT-1 和 mTOR 信号介导的代谢破坏诱导人肾细胞癌 786-O 细胞死亡
影响因子：
4.2
作者：
Li, Zeyan;Tang, Yueqing;Zhang, Wenhua
通讯作者：
Zhang, Wenhua