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LncRNA ZEB1-AS1/miR-1224-5p / MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistent Chlamydia

Fangzhen Luo1,2, Yating Wen1, Lanhua Zhao1

  • 1Institute of Pathogenic Biology, Hengyang Medical School, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, P. R. China.

Virulence
|March 10, 2022
PubMed

Insights

Persistent Chlamydia trachomatis infections resist cell death by inhibiting apoptosis. This study reveals the long non-coding RNA ZEB1-AS1 promotes this resistance via the miR-1224-5p/MAP4K4 axis and MAPK/ERK pathway, offering potential therapeutic targets.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Cell Biology

Background:

  • Persistent Chlamydia trachomatis infection causes severe health issues like blindness and infertility.
  • Chlamydia trachomatis evades host defenses by inhibiting apoptosis.
  • ZEB1-AS1, a long non-coding RNA (lncRNA), was previously found to be upregulated during persistent C. trachomatis infection.

Purpose of the Study:

  • To investigate the role of ZEB1-AS1 in persistent C. trachomatis infection.
  • To elucidate the molecular mechanisms by which ZEB1-AS1 influences apoptosis resistance.
  • To identify potential therapeutic strategies targeting ZEB1-AS1.

Main Methods:

  • Targeted silencing of ZEB1-AS1 in infected cells.
  • Analysis of apoptosis-related proteins (Bcl-2, Bax, cytochrome c) and caspase-3 activation.
  • Luciferase reporter assays to confirm interactions between ZEB1-AS1, miR-1224-5p, and MAP4K4.
  • Investigation of the MAPK/ERK pathway activation.

Main Results:

  • Silencing ZEB1-AS1 increased apoptosis rates in persistently infected cells.
  • ZEB1-AS1 interference decreased the Bcl-2/Bax ratio, reduced mitochondrial membrane potential, and increased caspase-3 activation.
  • ZEB1-AS1 functions as a molecular sponge for miR-1224-5p, targeting MAP4K4.
  • ZEB1-AS1 promotes apoptosis resistance by activating the MAPK/ERK pathway.

Conclusions:

  • The ZEB1-AS1/miR-1224-5p/MAP4K4 axis is a key mechanism for apoptosis resistance in persistent C. trachomatis infection.
  • ZEB1-AS1 contributes to pathogenesis by inhibiting host cell apoptosis through the MAPK/ERK pathway.
  • Targeting this axis presents a potential therapeutic strategy for persistent C. trachomatis infections.
Keywords:
Chlamydia trachomatisMAP4K4antiapoptosislncRNA ZEB1-AS1miR-1224-5ppersistent infection

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