Liposomal Delivery of miR-34b-5p Induced Cancer Cell Death in Thyroid Carcinoma.
Hamidreza MaroofFarhadul IslamLanFeng DongPrabha AjjikuttiraVinod GopalanNigel A J McMillanAlfred King-Yin LamPublished in: Cells (2018)
This study aims to determine the functional roles of microRNA-34b-5p (miR-34b) in the suppression of anaplastic thyroid carcinoma. We used hydration-of-freeze-dried-matrix (HFDM) formulated liposomes (liposome-loaded miR-34b) for effective delivery of miR-34b to anaplastic thyroid carcinoma in vitro and in vivo. Real time polymerase chain was used to determine the level of miR-34b. Immunocytochemistry, Western blot and ELISA were carried out to determine the effect of this manipulation on VEGF-A expression. In addition, an in vivo xenotransplantation mouse model was used to investigate the functional roles of overexpression of miR-34b in the carcinoma. In anaplastic thyroid carcinoma cells, miR-34b expression was low and significant overexpression (p < 0.05) was noted following transfection with liposome-loaded miR-34b. The miR-34b overexpressed thyroid carcinoma cell lines showed reduction in VEGF-A protein expression, decreased cell proliferation, decreased wound healing, reduced cell cycle progression and increased apoptosis (p < 0.05). In in vivo experiments, when compared to control groups, smaller tumours formed upon intravenous administration of liposome-loaded miR-34b. To conclude, the current study confirmed the tumour suppressor properties of miR-34b via VEGF-A regulation in anaplastic thyroid carcinoma. In addition, delivery of miR-34b using cationic liposome could be a useful therapeutic strategy for targeting therapy in the carcinoma.
Keyphrases
- cell proliferation
- cell cycle
- drug delivery
- wound healing
- cell death
- cancer therapy
- mouse model
- poor prognosis
- endothelial cells
- vascular endothelial growth factor
- oxidative stress
- transcription factor
- squamous cell carcinoma
- papillary thyroid
- endoplasmic reticulum stress
- young adults
- signaling pathway
- drug release
- low dose
- mesenchymal stem cells
- stress induced