Abstract
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.
Highlights
Anaplastic thyroid carcinoma of thyroid, known as undifferentiated thyroid carcinoma, is one of the most lethal human malignancies, with the most complex genetic make-up in thyroid carcinoma [1]
The results indicated that the prepared liposome-loaded miR-34b liposomes had favourable characteristics for effective delivery of miR-34b with high entrapment efficiency and size below 200 nm
The results indicated that the prepared liposome-loaded miR-34b liposomes have favourable characteristics for effective delivery of miR-34b such as high entrapment efficiency and size below 200 nm
Summary
Anaplastic thyroid carcinoma of thyroid, known as undifferentiated thyroid carcinoma, is one of the most lethal human malignancies, with the most complex genetic make-up in thyroid carcinoma [1]. It is worth noting that papillary thyroid carcinoma, the most common thyroid cancer, can dedifferentiate to anaplastic thyroid carcinoma [2,3]. The current treatment modalities are not effective for this type of thyroid cancer and only a small percentage of patients with carcinoma survive beyond two years [3,4]. To improve the quality of life of patients with anaplastic thyroid carcinoma, we need an understanding of the carcinogenesis to develop new modes of treatment for this carcinoma. Several microRNAs could suppress the progression of the carcinoma in vitro and in vivo [5,6,7]. Micro-34b-5p functions as a potent regulator of angiogenesis and have been reported to be involved in thyroid carcinoma [8,9,10]
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