piRNA PROPER Suppresses DUSP1 Translation by Targeting N6-Methyladenosine-Mediated RNA Circularization to Promote Oncogenesis of Prostate Cancer
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View abstract on PubMed
Summary
This summary is machine-generated.A novel piRNA variant, PROPER, increases prostate cancer (PCa) risk and metastasis by regulating DUSP1 expression. Targeting PROPER shows therapeutic potential for PCa prevention and treatment.
Area Of Science
- Oncology
- Molecular Biology
- Genetics
Background
- Genetic and epigenetic alterations are crucial in cancer development.
- Knowledge linking PIWI-interacting RNAs (piRNAs) and their variants to prostate cancer (PCa) risk and progression is limited.
Purpose Of The Study
- To investigate the role of piRNAs and their genetic variants in PCa.
- To identify specific piRNA genetic variants associated with PCa risk and progression.
Main Methods
- Combined three genome-wide association study datasets (85,707 PCa cases, 166,247 controls).
- Performed functional investigations using cellular and mouse models.
- Manipulated piRNA expression to study its oncogenetic role.
Main Results
- Identified a specific genetic variant (rs17201241) linked to increased PROPER (piRNA overexpressed in prostate cancer) expression in PCa tumors.
- PROPER promotes PCa metastasis by facilitating DUSP1 degradation via an m6A-dependent mechanism involving YTHDF2, EIF2S3, and YBX3.
- Inhibition of PROPER suppressed tumor growth in xenograft models.
Conclusions
- Targeting piRNA PROPER offers a promising strategy for PCa prevention and treatment.
- PROPER plays a significant oncogenetic role in PCa progression.
- Genetic and epigenetic fine control by piRNAs is a key factor in PCa development.
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