Impact of novel oncogenic pathways regulated by antitumor miR-451a in renal cell carcinoma
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Updated: Feb 14, 2026

Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Yasutaka Yamada1,2, Takayuki Arai1,2, Sho Sugawara1,2
1Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Abstract:
Recent analyses of our microRNA (miRNA) expression signatures obtained from several types of cancer have provided novel information on their molecular pathology. In renal cell carcinoma (RCC), expression of microRNA-451a (miR-451a) was significantly downregulated in patient specimens and low expression of miR-451a was significantly associated with poor prognosis of RCC patients (P = .00305) based on data in The Cancer Genome Atlas. The aims of the present study were to investigate the antitumor roles of miR-451a and to identify novel oncogenic networks it regulated in RCC cells. Ectopic expression of miR-451a significantly inhibited cancer cell migration and invasion by RCC cell lines, suggesting that miR-451a had antitumor roles. To identify oncogenes regulated by miR-451a in RCC cells, we analyzed genome-wide gene expression data and examined information in in silico databases. A total of 16 oncogenes and were found to be possible targets of miR-451a regulation. Interestingly, high expression of 9 genes (PMM2, CRELD2, CLEC2D, SPC25, BST2, EVL, TBX15, DPYSL3, and NAMPT) was significantly associated with poor prognosis. In this study, we focused on phosphomannomutase 2 (PMM2), which was the most strongly associated with prognosis. Overexpression of PMM2 was detected in clinical specimens and Spearman's rank test indicated a negative correlation between the expression levels of miR-451a and PMM2 (P = .0409). Knockdown of PMM2 in RCC cells inhibited cancer cell migration and invasion, indicating overexpression of PMM2 could promote malignancy. Analytic strategies based on antitumor miRNAs is an effective tool for identification of novel pathways of cancer.
Insights
MicroRNA-451a (miR-451a) is downregulated in renal cell carcinoma (RCC) and inhibits cancer cell migration. Its target, phosphomannomutase 2 (PMM2), promotes RCC malignancy, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) expression signatures offer insights into cancer molecular pathology.
- MicroRNA-451a (miR-451a) is downregulated in renal cell carcinoma (RCC) and linked to poor prognosis.
- Investigating miR-451a's role is crucial for understanding RCC progression.
Purpose of the Study:
- To investigate the antitumor roles of miR-451a in RCC.
- To identify novel oncogenic networks regulated by miR-451a in RCC cells.
Main Methods:
- Analysis of miRNA expression signatures from The Cancer Genome Atlas.
- Ectopic expression of miR-451a in RCC cell lines.
- Genome-wide gene expression data analysis and in silico database examination.
- Focus on phosphomannomutase 2 (PMM2) as a potential target.
Main Results:
- Ectopic miR-451a expression inhibited RCC cell migration and invasion.
- Sixteen potential oncogene targets of miR-451a were identified.
- High expression of PMM2 correlated with poor prognosis and was negatively correlated with miR-451a levels.
- PMM2 knockdown inhibited RCC cell migration and invasion.
Conclusions:
- miR-451a exhibits antitumor roles in RCC by suppressing cell migration and invasion.
- PMM2 is identified as a novel oncogene regulated by miR-451a, promoting RCC malignancy.
- Antitumor miRNA-based strategies are effective for identifying novel cancer pathways.
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