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

Abstract

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.

Cancer-Associated Fibroblasts Promote Migration and Invasion of Non-Small Cell Lung Cancer Cells via miR-101-3p Mediated VEGFA Secretion and AKT/eNOS Pathway

“…In particular, miRNAs are also involved in tumor invasion and metastasis. MiR-153-5p promotes the proliferation and metastasis via targeting AGO1 in renal cell carcinoma ( Li et al, 2021 ), our previous study demonstrated that miR-26a enhances invasiveness of human lung cancer cells by suppressing GSK3β ( Lin et al, 2017 ). On the contrary, miRNAs may also inhibit metastasis.…”

The Ambivalent Role of miRNAs in Carcinogenesis: Involvement in Renal Cell Carcinoma and Their Clinical Applications

“…A recent study identified miR-153-5p as responsible for ccRCC occurrence and progression. The upregulation of miR-153-5p and the relative downregulation of its target AGO1 correlate with increased proliferation and metastatization of ccRCC by activating PI3K/Akt signaling [83].…”

Circulating microRNAs from the Molecular Mechanisms to Clinical Biomarkers: A Focus on the Clear Cell Renal Cell Carcinoma

“…The mechanism involves the targeting of AGO1, a key protein physiologically participating in mechanisms of RNA silencing, including miRNAs [131] and a predictive marker of ccRCC [132]. The miR-153-5p/AGO1 axis has been demonstrated to act through the PI3K/AKT pathway, and therefore fostering tumor growth and progression [133].…”