Abstract
Background: Colorectal cancer (CRC) is a malignancy with high mortality. TSPYL2 participates in tumor suppression but its role in CRC remains unknown. Methodology & results: TSPYL2 was downregulated and SIRT1 was upregulated in gefitinibdrug-resistant(GEF-DR) tissues of patients withCRC. The GEF-resistant cells, HCT116 and HCT-15, were successfully established. The knockdown of TSPYL2 promotedresistance to GEF in CRC cells. Interestingly, immunofluorescence and western blot assays demonstrated that TSPYL2 inhibited DNA damage repair in HCT-15 and HCT116 GEF-resistant cells. Mechanically, TSPYL2 reduced the resistance to GEF and inhibited DNA damage repair via suppressing SIRT1-mediated FOXO3 deacetylation. TSPYL2 consistentlyinhibited tumor growth and decreasedresistance to GEF in vivo. Conclusion: TSPYL2 reduced resistance to GEF and suppressed DNA damage through downregulating SIRT1-mediated FOXO3 deacetylation, indicating that TSPYL2 might be a novel therapeutic target in CRC.
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