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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
RIOK2 Promotes Clear Cell Renal Cell Carcinoma Progression Through Cell Cycle Regulation
Hiroyuki Shikuma1, Keisuke Goto1, Ayako Shimo1
1Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
High expression of Right Open Reading Frame Kinase 2 (RIOK2) in clear cell renal cell carcinoma (ccRCC) correlates with aggressive disease and poor survival. Inhibiting RIOK2 suppressed tumor cell proliferation and migration, suggesting RIOK2 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype, often linked to poor patient outcomes.
- Ribosome biogenesis is upregulated in many cancers, promoting tumor cell proliferation.
- The role of Right Open Reading Frame Kinase 2 (RIOK2), crucial for 40S ribosomal subunit maturation, in ccRCC was previously unexplored.
Purpose of the Study:
- To investigate the clinical significance and biological role of RIOK2 in ccRCC.
- To determine the association between RIOK2 expression and ccRCC patient prognosis.
- To explore the functional impact of RIOK2 on ccRCC cell behavior and the cell cycle.
Main Methods:
- Immunohistochemical analysis of 166 ccRCC specimens.
- Analysis of public ccRCC datasets for RIOK2 mRNA expression and prognostic correlation.
- In vitro functional studies including RIOK2 knockdown, RNA sequencing, gene set enrichment analysis, and flow cytometry.
- Assessment of a small-molecule RIOK2 inhibitor (NSC139021).
Main Results:
- High RIOK2 expression in ccRCC tissues correlated with advanced pathological stage, higher tumor grade, and reduced cancer-specific and progression-free survival.
- Public datasets confirmed elevated RIOK2 mRNA in ccRCC and its association with poor prognosis.
- RIOK2 knockdown inhibited ccRCC cell proliferation, invasion, and migration, leading to G1 cell cycle arrest and downregulation of cell cycle-related pathways (e.g., E2F targets, G2/M checkpoint).
- The RIOK2 inhibitor NSC139021 suppressed ccRCC cell proliferation.
Conclusions:
- RIOK2 is upregulated in ccRCC and serves as a clinically relevant biomarker for aggressive disease.
- RIOK2 plays a critical role in ccRCC cell proliferation and cell cycle regulation.
- Targeting RIOK2 may represent a promising therapeutic strategy for ccRCC.
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