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MiR-342-3p inhibits LCSC oncogenicity and cell stemness through HDAC7/PTEN axis

Chunlin Xu1, Weiwei Sun2, Jinglei Liu2

  • 1Department of Infectious Disease (No. 3), Second Affiliated Hospital of Harbin Medical University, Harbin, 150040, Heilongjiang, People's Republic of China.

Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
|November 29, 2021
PubMed
Abstract

Insights

MicroRNA-342-3p (miR-342-3p) inhibits liver cancer stem cells (LCSC) by targeting HDAC7 and promoting PTEN. This finding offers a potential therapeutic strategy for liver cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Liver cancer stem cells (LCSC) are crucial drivers of tumor initiation, progression, and therapeutic resistance.
  • Understanding the molecular mechanisms regulating LCSC stemness is vital for developing effective liver cancer treatments.

Purpose of the Study:

  • To investigate the role of miR-342-3p in regulating the biological behavior and molecular mechanisms of liver cancer stem cells (LCSC).

Main Methods:

  • LCSC were isolated and characterized using flow cytometry and immunomagnetic beads.
  • Self-renewal and growth capacities were assessed via spheroid and soft agar assays.
  • Expression levels of stemness markers (CD44, ALDH1, Bmi1, Sox2, Oct4) were analyzed by Western blot and qPCR.
  • The interaction between miR-342-3p and HDAC7 was validated using a dual-luciferase reporter assay.

Main Results:

  • Overexpression of miR-342-3p significantly reduced LCSC tumor volume, spheroid formation, and colony formation rates.
  • miR-342-3p suppressed the expression of key stemness markers (CD44, ALDH1, Bmi1, Sox2, Oct4).
  • HDAC7 was identified as a direct target of miR-342-3p; its inhibition or PTEN overexpression reduced LCSC stemness. HDAC7 promoted H3 deacetylation and suppressed PTEN expression.

Conclusions:

  • MiR-342-3p exerts an inhibitory effect on liver cancer stem cell oncogenicity and stemness.
  • This inhibition is mediated through the promotion of PTEN expression and the suppression of HDAC7.
  • Targeting the miR-342-3p/HDAC7/PTEN axis represents a promising therapeutic strategy for liver cancer.
Keywords:
Cell stemnessHDAC7Liver cancer stem cellsMiR-342-3pOncogenicityPTEN

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