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MiR-92 overexpression suppresses immune cell function in ovarian cancer via LATS2/YAP1/PD-L1 pathway

S Feng1, H Sun1, W Zhu2

  • 1Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu Province, People's Republic of China.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|July 13, 2020
PubMed
Abstract

Insights

MicroRNA-92 (miR-92) is overexpressed in ovarian cancer, promoting tumor growth and immune suppression by targeting LATS2, leading to increased PD-L1 and reduced NK cell function.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • MicroRNAs (miRNAs) are critical regulators in various cancers, including ovarian cancer.
  • Dysregulation of miRNA expression is implicated in ovarian cancer pathogenesis and progression.

Purpose of the Study:

  • To investigate the role of microRNA-92 (miR-92) in ovarian cancer.
  • To elucidate the underlying molecular mechanisms by which miR-92 influences ovarian cancer progression and immune evasion.

Main Methods:

  • Quantitative analysis of miR-92 expression in clinical ovarian cancer tissues.
  • In vitro functional assays to assess the impact of miR-92 on cancer cell proliferation, migration, and colony formation.
  • Molecular mechanism studies using luciferase assays, co-immunoprecipitation (Co-IP), and chromatin immunoprecipitation (ChIP) to identify miR-92 targets and downstream pathways.

Main Results:

  • miR-92 is significantly overexpressed in ovarian cancer tissues compared to normal tissues.
  • miR-92 promotes ovarian cancer cell proliferation, migration, and colony formation.
  • miR-92 directly targets LATS2, leading to its downregulation.
  • Downregulation of LATS2 results in YAP1 translocation, PD-L1 upregulation, and subsequent suppression of Natural Killer (NK) cell function and promotion of T cell apoptosis.
  • YAP1 binds to the enhancer region of PD-L1, enhancing its transcription.

Conclusions:

  • miR-92 plays a crucial oncogenic role in ovarian cancer.
  • A novel mechanism involving miR-92, LATS2, YAP1, and PD-L1 contributes to immune suppression in ovarian cancer.
Keywords:
LATS2MiR-92Ovarian cancerPD-L1YAP1

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