PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Clear-cell renal cell carcinoma (ccRCC) is a common malignancy with a high rate of metastasis.
• Piwi-interacting RNAs (piRNAs) are increasingly recognized for their roles in various cancers, but their specific mechanisms in ccRCC remain underexplored.

Purpose of the Study:

• To identify and characterize the role of differentially expressed piRNAs in ccRCC metastasis.
• To elucidate the molecular mechanism by which piR-57125 influences ccRCC progression.

Main Methods:

• piRNA-sequencing and TCGA data analysis to identify differentially expressed piRNAs in ccRCC.
• In vitro assays (cell migration and invasion) and in vivo lung metastasis models to assess piR-57125 function.
• Luciferase reporter assays and Western blotting to confirm direct targeting of CCL3 and pathway modulation.

Main Results:

• PiR-57125 was significantly downregulated in ccRCC tissues.
• Knockdown of piR-57125 enhanced ccRCC cell migration and invasion, while overexpression suppressed metastasis.
• CCL3 was identified as a direct target of piR-57125, and piR-57125 modulated ccRCC metastasis via the AKT/ERK pathway.

Conclusions:

• PiR-57125 acts as a tumor suppressor in ccRCC by inhibiting metastasis.
• PiR-57125 restrains ccRCC metastasis through direct targeting of CCL3 and regulation of the AKT/ERK pathway.
• PiR-57125 represents a potential therapeutic target for managing ccRCC metastasis.