Abstract

Introduction Mounting evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and progression. Objectives This study aimed to elucidate the role of AC007637.1 , a lncRNA downregulated in colorectal cancer (CRC) identified by our previous transcriptomic analyses. Methods AC007637.1 expression in CRC was assessed via bioinformatic analysis and qRT-PCR. The effects of AC007637.1 on CRC tumorigenesis were evaluated using CCK-8 assays, colony formation assays and tumor xenograft models. RNA immunoprecipitation, RNA pull-down, and co-immunoprecipitation assays were utilized to clarify the molecular mechanism of AC007637.1 in CRC. Results AC007637.1 serves as a tumor suppressor by inhibiting CRC proliferation and tumorigenicity. It directly binds to proliferating cell nuclear antigen (PCNA) and promotes Tripartite motif-containing 25 (Trim25)-mediated PCNA ubiquitination and subsequent proteasomal degradation, thereby inhibiting DNA replication and repair pathways and enhancing cancer cell sensitivity to DNA-damage-related therapies. In addition, the stability of AC007637.1 is reduced by fragile X-related protein-1 (FXR1) and its transcription is inhibited by promoter hypermethylation. Conclusions We identify a novel AC007637.1 /Trim25/PCNA regulatory axis in CRC, providing valuable insights into the molecular pathogenesis of this disease. This axis represents a   promising therapeutic target for CRC.