Impact of novel oncogenic pathways regulated by antitumor miR-451a in renal cell carcinoma

Yasutaka Yamada1,2, Takayuki Arai1,2, Sho Sugawara1,2

  • 1Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.

Cancer Science
|February 9, 2018
PubMed

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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