biostudies-literatureRisner ANCATS NIH HHSMedical University of South CarolinaNIDDK NIH HHSNCI NIH HHSNIGMS NIH HHSbio061942https://www.ebi.ac.uk/biostudies/studies/S-EPMC12444863biostudies-literatureUnknown14(9)Reactivation of transposable elements (TEs) in somatic tissues, particularly of LINE-1, is associated with disease by causing gene mutations and DNA damage. Previous work has shown that the PIWI pathway is crucial for TE suppression in the germline. However, the status and function of this pathway is not well characterized in differentiated somatic cells and there is a lack of consensus on the role of the pathway in somatic tumorigenesis. To shed light on this conundrum, we examined the PIWI pathway in colon cancer through combining bioinformatic analyses and cell-based assays. Shifted weighted annotation network (SWAN) analysis revealed that the pathway experiences significant allelic losses in colon cancer and that PIWIL2, the main catalytic component of the pathway responsible for TE siBiology openPIWIL2 downregulation in colon cancer promotes transposon activity and pro-tumorigenic phenotypes.PMC12444863R01 GM160815UL1 TR001450R01 GM130846DP2 CA280626T32 5T32DK124191R01 DK124553R21 CA246233T32 DK124191R01 DK136658F31 DK138780TL1 TR001451P20 GM130457P30 DK123704Gangaraju VDelaney JRCheedipudi ARisner AKourtidis ANair-Menon JfalsePIWIL2 downregulation in colon cancer promotes transposon activity and pro-tumorigenic phenotypes.Reactivation of transposable elements (TEs) in somatic tissues, particularly of LINE-1, is associated with disease by causing gene mutations and DNA damage. Previous work has shown that the PIWI pathway is crucial for TE suppression in the germline. However, the status and function of this pathway is not well characterized in differentiated somatic cells and there is a lack of consensus on the role of the pathway in somatic tumorigenesis. To shed light on this conundrum, we examined the PIWI pathway in colon cancer through combining bioinformatic analyses and cell-based assays. Shifted weighted annotation network (SWAN) analysis revealed that the pathway experiences significant allelic losses in colon cancer and that PIWIL2, the main catalytic component of the pathway responsible for TE si2025-01-01T00:00:00Z2025 Sep2026-06-03T15:29:39.461Z2026-04-29T03:12:38.999ZS-EPMC124448634078916410.1242/bio.061942