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Published on: August 2, 2024
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.
Abstract:
Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play critical roles in human diseases. We aimed to clarify the role of lncRNA X-inactive specific transcript (XIST)/miR-149-3p/forkhead box P3 (FOXP3) axis in ovarian cancer (OC) cell growth. XIST, miR-149-3p and FOXP3 expression in OC tissues and cell lines was assessed, and the predictive role of XIST in prognosis of OC patients was analyzed. The OC cell lines were screened and accordingly treated with silenced/overexpressed XIST plasmid or miR-149-3p mimic/inhibitor, and then the proliferation, invasion, migration, colony formation ability, apoptosis, and cell cycle distribution of OC cells were measured. Effect of altered XIST and miR-149-3p on tumor growth in vivo was observed. Online website prediction and dual luciferase reporter gene were implemented to detect the targeting relationship of lncRNA XIST, miR-149-3p, and FOXP3. XIST and FOXP3 were upregulated, whereas miR-149-3p was downregulated in OC tissues and cells. High XIST expression indicated a poor prognosis of OC. Inhibition of XIST or elevation of miR-149-3p repressed proliferation, invasion, migration, and colony formation ability, and promoted apoptosis and cell cycle arrest of HO-8910 cells. In SKOV3 cells upon treatment of overexpressed XIST or reduction of miR-149-3p, there exhibited an opposite tendency. Based on online website prediction, dual luciferase reporter gene, and RNA pull-down assays, we found that there was a negative relationship between XIST and miR-149-3p, and miR-149-3p downregulated FOXP3 expression. This study highlights that knockdown of XIST elevates miR-149-3p expression to suppress malignant behaviors of OC cells, thereby inhibiting OC development.
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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