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Human Bone Marrow Mesenchymal Stem Cell (hBMSCs)-Derived miR-29a-3p-Containing Exosomes Impede Laryngocarcinoma Cell
Tingting Yu1, Hong Yu1, Dong Xiao1
1Department of Otolaryngology, Head and Neck Surgery, The First Hospital, Jilin University, Changchun, Jilin, China.
Abstract:
Although microRNA-29a-3p was reported to inhibit laryngocarcinoma progression, the potential mechanisms have not been explored clearly. Laryngocarcinoma tissues were collected for analyzing the levels of miR-29a-3p and phosphatase and tensin homolog (PTEN). The miR mimics or inhibitor was transfected into laryngocarcinoma cell lines M4E and Hep2 for the investigation of the biological functions (proliferative, invasion, migratory rates, and apoptotic rates) of this miRNA. The exosomes (Exo) from human bone marrow mesenchymal stem cells (hBMSCs) after the transfection of miR mimics/inhibitor/si-PTEN were isolated and used to stimulate M4E and Hep2 cells. The in vivo mouse model was constructed to verify our findings. The miR-29a-3p level was decreased, and PTEN level was elevated in laryngocarcinoma tissues and the cancer cell lines. MiR mimics could inhibit proliferative, invasive migratory rates while promoting apoptotic rates of M4E and Hep2 cells. MiR-29a-3p was enriched in hBMSC-derived Exo, and the Exo from miR-29a-3p mimics transfected hBMSCs could inhibit laryngocarcinoma cell malignant phenotypes in vitro and prevent tumor progression in vivo. In addition, the direct binding relationship between miR-29a-3p and PTEN in this disease was determined. In conclusion, hBMSC-derived Exo with upregulated miR-29a-3p inhibited laryngocarcinoma progression via regulating PTEN, providing a potential diagnostic and therapeutic target in this disease.
Insights
Upregulated microRNA-29a-3p, delivered via mesenchymal stem cell exosomes, inhibits laryngocarcinoma progression by targeting PTEN. This discovery offers a potential new diagnostic and therapeutic strategy for laryngocarcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Laryngocarcinoma progression mechanisms are not fully understood.
- The role of microRNA-29a-3p in laryngocarcinoma requires further elucidation.
- Phosphatase and tensin homolog (PTEN) is a key tumor suppressor.
Purpose of the Study:
- To investigate the inhibitory mechanisms of microRNA-29a-3p in laryngocarcinoma.
- To explore the potential of human bone marrow mesenchymal stem cell (hBMSC)-derived exosomes as a delivery vehicle for microRNA-29a-3p.
- To determine the relationship between microRNA-29a-3p and PTEN in laryngocarcinoma.
Main Methods:
- Analysis of miR-29a-3p and PTEN levels in laryngocarcinoma tissues and cell lines.
- Transfection of miR mimics/inhibitor into laryngocarcinoma cell lines (M4E, Hep2).
- Isolation and characterization of exosomes from hBMSCs engineered to overexpress miR-29a-3p.
- In vitro functional assays (proliferation, invasion, migration, apoptosis) and in vivo mouse models.
Main Results:
- Laryngocarcinoma tissues and cells showed decreased miR-29a-3p and elevated PTEN levels.
- miR-29a-3p mimics inhibited cancer cell proliferation, invasion, and migration, while promoting apoptosis.
- hBMSC-derived exosomes enriched with miR-29a-3p suppressed laryngocarcinoma cell malignancy in vitro and tumor growth in vivo.
- A direct binding interaction between miR-29a-3p and PTEN was confirmed.
Conclusions:
- Upregulated miR-29a-3p delivered via hBMSC-derived exosomes inhibits laryngocarcinoma progression.
- The mechanism involves the regulation of PTEN by miR-29a-3p.
- This exosome-based miR-29a-3p delivery represents a promising therapeutic strategy for laryngocarcinoma.
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