Inhibition of long non-coding RNA XIST upregulates microRNA-149-3p to repress ovarian cancer cell progression

Rong Jiang1, Hongyu Zhang1, Jinhua Zhou1

  • 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China.

Cell Death & Disease
|February 5, 2021
PubMed

Insights

Long non-coding RNA XIST and FOXP3 are elevated in ovarian cancer, while miR-149-3p is decreased. Inhibiting XIST or boosting miR-149-3p suppresses ovarian cancer cell growth and progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are key regulators in human diseases.
  • The specific roles of the XIST/miR-149-3p/FOXP3 axis in ovarian cancer (OC) require further elucidation.

Purpose of the Study:

  • To investigate the functional role of the lncRNA XIST/miR-149-3p/FOXP3 regulatory pathway in ovarian cancer progression.
  • To determine the prognostic value of XIST in ovarian cancer patients.

Main Methods:

  • Expression analysis of XIST, miR-149-3p, and FOXP3 in OC tissues and cell lines.
  • In vitro functional assays (proliferation, invasion, migration, colony formation, apoptosis, cell cycle) after manipulating XIST and miR-149-3p levels.
  • In vivo tumor growth assessment.
  • Bioinformatic predictions and dual-luciferase reporter assays to confirm molecular interactions.

Main Results:

  • XIST and FOXP3 were significantly upregulated, while miR-149-3p was downregulated in OC tissues and cells.
  • High XIST expression correlated with poor prognosis in OC patients.
  • Knockdown of XIST or overexpression of miR-149-3p inhibited OC cell proliferation, invasion, and migration, and promoted apoptosis and cell cycle arrest.
  • miR-149-3p directly targets and downregulates FOXP3 expression, with XIST negatively regulating miR-149-3p.

Conclusions:

  • The XIST/miR-149-3p/FOXP3 axis is a critical regulator of ovarian cancer cell growth and malignancy.
  • Targeting XIST or modulating miR-149-3p levels offers a potential therapeutic strategy for ovarian cancer by suppressing tumor progression.

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