4.7 Article

MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1

Journal

CELL DEATH & DISEASE
Volume 12, Issue 1, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1038/s41419-020-03306-y

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Funding

  1. National Natural Science Foundation of China [81672522]
  2. Cheeloo College of Medicine of Shandong University-Karolinska Institute Cooperative Research Projects [SDU-KI-2020-8, SDU-KI-2020-10]
  3. Cheeloo College of Medicine of Shandong University- Karolinska Institute Cooperative Research Projects [SDU-KI-2020-8, SDU-KI-2020-10]

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The study identified the miR-153-5p/AGO1 axis as crucial in the occurrence and progression of ccRCC tumors through the PI3K/Akt signaling pathway, providing potential therapeutic targets and prognostic biomarkers for patients with ccRCC.
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.

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