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MicroRNA-155-5p Targets JADE-1, Promoting Proliferation, Migration, and Invasion in Clear Cell Renal Cell Carcinoma
Thomas Kalantzakos1, Kailey Hooper1, Sanjna Das1
1Department of Translational Research, Lahey Hospital and Medical Center, Burlington, MA 01805, USA.
International Journal of Molecular Sciences
|May 13, 2023
Summary
Overexpression of microRNA-155-5p (miR-155-5p) promotes aggressive clear cell renal cell carcinoma (ccRCC) by downregulating the tumor suppressor Jade-1. Inhibiting miR-155-5p reduced tumor growth and metastasis in ccRCC models.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) incidence is increasing, with microRNA (miRNA) expression linked to cancer progression.
- miR-155-5p is overexpressed in ccRCC and associated with aggressive cancer phenotypes.
- Jade-1, a tumor suppressor, is regulated by Von-Hippel Lindau (VHL), frequently mutated in ccRCC.
Purpose of the Study:
- To investigate the role of miR-155-5p and its target Jade-1 in ccRCC pathogenesis.
- To elucidate the mechanism by which miR-155-5p drives aggressive ccRCC phenotypes.
Main Methods:
- Downregulation of miR-155-5p in ccRCC cell lines (786-O, Caki-1).
- Knockdown of Jade-1 using shRNA in ccRCC cell lines.
- In vivo studies using a mouse xenograft model.
- 3'UTR luciferase reporter assay to confirm direct interaction.
Main Results:
- Downregulation of miR-155-5p in ccRCC cells reduced oncogenic potential and increased Jade-1 levels.
- Jade-1 knockdown in ccRCC cells increased proliferation, migration, and invasion.
- In vivo, miR-155 downregulation decreased tumor implantation and proliferation rates.
- Direct interaction between miR-155-5p and Jade-1 was confirmed.
Conclusions:
- miR-155-5p promotes ccRCC aggressiveness by suppressing Jade-1.
- Targeting miR-155-5p may offer a therapeutic strategy for aggressive ccRCC.
- Understanding the miR-155-5p/Jade-1 axis is crucial for ccRCC treatment.
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