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Nucleus-localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG

Meiliang Liu1,2, Mingshuang Lai1,2, Deyuan Li1,2

  • 1Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, China.

Cancer Science
|August 7, 2023
PubMed

Insights

Circular RNA circSLC39A5 is downregulated in hepatocellular carcinoma (HCC) and acts as a potential diagnostic marker. This nucleus-localized circular RNA inhibits HCC progression by regulating the STAT1/TDG/PCNA pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
  • The specific functions and mechanisms of nuclear-localized circRNAs in hepatocellular carcinoma (HCC) remain largely unexplored.

Purpose of the Study:

  • To investigate the expression, diagnostic value, and functional mechanism of circSLC39A5 in HCC.
  • To elucidate the role of nuclear circSLC39A5 in regulating HCC cell behavior and gene expression.

Main Methods:

  • Quantitative reverse transcription-PCR (qRT-PCR) and receiver-operating characteristic (ROC) curve analysis for expression and diagnosis.
  • In vitro and in vivo experiments to assess biological function.
  • Nucleoplasmic separation, FISH, RNA pulldown, RIP, HDOCK, NucleicNet, CLIP, MG132 treatment, and ChIP to explore molecular mechanisms.

Main Results:

  • circSLC39A5 was significantly downregulated in HCC tissues and plasma, correlating with metastasis.
  • circSLC39A5 demonstrated high diagnostic potential for HCC (AUC=0.915) and stability in plasma.
  • circSLC39A5 inhibited HCC proliferation, migration, and invasion, while promoting apoptosis, by interacting with STAT1 to regulate TDG/PCNA expression.

Conclusions:

  • circSLC39A5 is a potential circulating biomarker for HCC diagnosis.
  • Nuclear circSLC39A5 plays a tumor-suppressive role in HCC through the STAT1/TDG/PCNA pathway, offering novel mechanistic insights.
Keywords:
STAT1circSLC39A5hepatocellular carcinomaplasmatranscriptional regulation

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