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CircMEG3 inhibits telomerase activity by reducing Cbf5 in human liver cancer stem cells

Xiaoxue Jiang1, Libo Xing1, Yingjie Chen1

  • 1Shanghai Putuo District People's Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China.

Molecular Therapy. Nucleic Acids
|January 11, 2021
PubMed

Insights

Circular RNA CircMEG3 is downregulated in liver cancer and inhibits cancer stem cell growth. It suppresses telomerase activity by regulating METTL3 and Cbf5, offering potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Circular RNAs (CircRNAs) are novel non-coding RNAs regulating gene expression.
  • CircRNAs play roles in various disease progressions.
  • Liver cancer remains a significant global health challenge.

Purpose of the Study:

  • To investigate the role of CircMEG3 in human liver cancer.
  • To elucidate the mechanism by which CircMEG3 affects liver cancer stem cells.
  • To identify potential therapeutic targets for liver cancer.

Main Methods:

  • Quantitative real-time PCR to measure CircMEG3 and Cbf5 expression.
  • In vitro and in vivo assays to assess the effect of CircMEG3 on cancer stem cell growth.
  • Western blotting to analyze protein expression levels (METTL3, Cbf5).

Main Results:

  • CircMEG3 expression is downregulated in human liver cancer and negatively correlated with Cbf5.
  • CircMEG3 inhibits the growth and malignant differentiation of liver cancer stem cells in vitro and in vivo.
  • CircMEG3 suppresses telomerase activity and shortens telomere length via the HULC-METTL3-Cbf5 pathway.
  • Increased Cbf5 expression counteracts the inhibitory effects of CircMEG3.

Conclusions:

  • CircMEG3 acts as a tumor suppressor in human liver cancer.
  • The HULC-METTL3-Cbf5 pathway is crucial for CircMEG3's function in regulating telomerase.
  • CircMEG3 and its regulatory pathway represent promising therapeutic targets for liver cancer treatment.
Keywords:
Cbf5CircMEG3HULCMETTL3liver cancer stem cellstelomere

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