piR-61298 promotes colorectal cancer progression through destabilizing p53 by interacting with USP10

PIWI-interacting RNAs (piRNAs) are a class of noncoding RNAs primarily found in germ cells. While piRNAs are known to be involved in various cancers, their specific roles in colorectal cancer (CRC) remain unclear. To elucidate the role of piRNAs in CRC, we first analyzed their expression characteristics by sequencing 10 pairs of tumor and adjacent normal tissues. Subsequently, differentially expressed piRNAs were identified through two-stage qRT-PCR validation using 20 and 114 pairs of samples. Subcellular localization was assessed through nucleoplasmic separation and immunofluorescence staining assays. RNA pull-down mass spectrometry was employed to identify piRNA-interacting proteins. We identified piR-61298as a piRNA significantly upregulated in CRC. Functional assays showed that piR-61298promoted cell proliferation and migration, inhibited apoptosis, and promoted tumor growth. Mechanistically, piR-61298bound to USP10 in the cytoplasm, impairing its deubiquitinating activity toward p53, thereby leading to p53 ubiquitination and degradation. These findings suggest that piR-61298plays a critical role in CRC progression by disrupting the USP10-p53 axis. Collectively, our study highlights piR-61298as a potential therapeutic target, offering a novel approach for CRC treatment by targeting piRNA-mediated regulation.