Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Laboratory of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
Cell Death Dis. 2021 Jan 4;12(1):33. doi: 10.1038/s41419-020-03306-y.
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.
微小 RNA（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，从转移、预后和与正常组织的差异表达三个方面筛选 ccRCC 中的差异表达 miRNA。miR-153-5p 被鉴定为促进 ccRCC 发生和进展的候选 miRNA。临床上，我们发现 miR-153-5p 在 ccRCC 中显著上调，并与不利的临床特征相关。此外，miR-153-5p 是一个独立的预后生物标志物。功能上，miR-153-5p 的耗竭通过磷脂酰肌醇 3-激酶（PI3K）/Akt 信号显著抑制 ccRCC 的增殖和转移。此外，AGO1 被证明是 miR-153-5p 的直接靶标。AGO1 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 AGO1 敲低显著促进肿瘤增殖和转移。AGO1 的下调部分消除了 miR-153-5p 敲低的致癌作用。此外，miR-153-5p 与 AGO1 联合显示出在 ccRCC 中更强大的预后意义。总之，我们发现新鉴定的 miR-153-5p/AGO1 轴通过 PI3K/Akt 信号通路负责肿瘤的发生和进展，因此可能为 ccRCC 患者提供有前途的治疗靶点和预后生物标志物。
