AI Article Synopsis
- Cervical cancer can result from persistent HPV infections, and the study explores the effects of human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEV) on HPV-positive cervical precancerous lesion cells.
- In experiments, hucMSC-sEV was found to significantly inhibit the growth and movement of S12 cells, with a key microRNA, miR-370-3p, identified as crucial for these effects by targeting the gene DHCR24.
- The research indicates that targeting DHCR24 through miR-370-3p can lower cholesterol levels in cells, thereby providing potential new treatment insights for cervical cancer prevention.
Article Abstract
Background: Cervical cancer is often caused by persistent high-risk human papillomavirus (HPV) infection, causing precancerous lesions. Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEV) exhibit diverse effects on tumors. This study investigates hucMSC-sEV, the impact and mechanisms on HPV-positive cervical precancerous lesion cells to provide new treatment insights.
Materials And Methods: We previously obtained hucMSC and hucMSC-sEV. In vitro experiments evaluated hucMSC-sEV effects on the proliferation and migration of S12 cells (derived from cervical precancerous lesions). Bioinformatics identified key microRNA components, and their impact on S12 cell proliferation and migration was investigated. The target gene of the microRNA component was predicted and confirmed via bioinformatics and dual-luciferase reporter assays. Lentiviral systems overexpressed target gene in S12 cells to examine the effects on microRNA impacts. SH-42 inhibitor was used to investigate target gene treatment potential. Immunohistochemistry assessed target gene expression in cervical precancerous lesions tissue.
Results: hucMSC-sEV significantly inhibited S12 cell proliferation and migration. Bioinformatics identified miR-370-3p as an effective cargo, which also suppressed S12 cell proliferation and migration. miR-370-3p was confirmed targeting DHCR24 (24-Dehydrocholesterol Reductase). DHCR24 overexpression reversed miR-370-3p's inhibitory effects, while SH-42 counteracted DHCR24 overexpression's promoting effects. Clinical specimen analysis supported these findings, demonstrating a positive correlation between DHCR24 protein expression and cervical precancerous lesions' progression.
Conclusions: hucMSC-sEV inhibits S12 cell proliferation and migration, mediated by miR-370-3p targeting DHCR24 to regulate cellular cholesterol content. DHCR24 inhibition reduces the cholesterol level and cell functions, suggesting its potential as a therapeutic target in cervical precancerous lesions.
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Article Synopsis
- The research included 96 patients, with a focus on 43 individuals diagnosed with both HIV and cervical cancer or precancerous conditions, analyzing RNA from their tissues to determine HPV expression.
- Results showed HIV-positive patients had a higher rate of integrated HPV-16 infections linked to lower CD4+ T cell counts, suggesting that HIV-related immunosuppression increases the progression of cervical lesions, emphasizing the need for better screening and treatment for HIV-positive women.
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