Long noncoding RNA AC007637.1 inhibits tumorigenesis by regulating the Trim25/PCNA axis in colorectal cancer

  • J Adv Res. 2026 Apr 6:S2090-1232(26)00306-1. doi: 10.1016/j.jare.2026.04.027.
Xue Wang  1 ,  Jiuming Li  1 ,  Chu Hao  2 ,  Kaisa Cui  3 ,  Lu Tian  2 ,  Jing Zhao  1 ,  Chaoqun Li  1 ,  Yuyang Feng  2 ,  Surui Yao  1 ,  Bojian Fei  4 ,  Xinliang Mao  5 ,  Zhaohui Huang  6
Affiliations
  • 1. Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China.
  • 2. Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China.
  • 3. Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, China.
  • 4. Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, China.
  • 5. Guangdong Provincial Key Lab of Protein Modification and Degradation, Guangzhou Medical University, Guangzhou 511436, China.
  • 6. Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address: [email protected].
PMID: 41951040 DOI: 10.1016/j.jare.2026.04.027
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 apromising therapeutic target for CRC.

Keywords
AC007637.1; Colorectal cancer; DNA repair; Long non-coding RNAs; PCNA; Trim25.
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