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

Xue Wang1, Jiuming Li1, Chu Hao2

  • 1Wuxi 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.

Abstract

Insights

This study reveals long noncoding RNA AC007637.1 acts as a tumor suppressor in colorectal cancer (CRC). It inhibits cancer growth by targeting the PCNA protein, offering a potential new therapeutic strategy for CRC.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
  • Colorectal cancer (CRC) progression is influenced by various genetic and epigenetic factors.
  • Previous transcriptomic analyses identified AC007637.1 as a downregulated lncRNA in CRC.

Purpose of the Study:

  • To investigate the function of the lncRNA AC007637.1 in colorectal cancer.
  • To elucidate the molecular mechanisms underlying AC007637.1's role in CRC pathogenesis.
  • To evaluate AC007637.1 as a potential therapeutic target for CRC.

Main Methods:

  • Assessed AC007637.1 expression using bioinformatic analysis and qRT-PCR.
  • Evaluated the impact of AC007637.1 on CRC cell proliferation and tumor growth in vitro and in vivo.
  • Utilized molecular assays (RIP, pull-down, co-IP) to determine the interaction between AC007637.1, PCNA, and Trim25.

Main Results:

  • AC007637.1 functions as a tumor suppressor, inhibiting CRC cell proliferation and tumorigenicity.
  • AC007637.1 directly binds to PCNA, promoting its ubiquitination and degradation via Trim25.
  • This interaction inhibits DNA replication/repair, sensitizing cancer cells to DNA-damage therapies; FXR1 reduces AC007637.1 stability, and hypermethylation inhibits its transcription.

Conclusions:

  • Identified a novel AC007637.1/Trim25/PCNA regulatory axis critical to CRC molecular pathogenesis.
  • AC007637.1 acts as a tumor suppressor by destabilizing PCNA.
  • This regulatory axis presents a promising therapeutic target for colorectal cancer treatment.

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