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Interactions of Vascular Endothelial Growth Factor and p53 with miR-195 in Thyroid Carcinoma: Possible Therapeutic Targets in Aggressive Thyroid Cancers

[ Vol. 18 , Issue. ]

Author(s):

Hamidreza Maroof , Soussan Irani , Armin Ariana, Jelena Vider, Vinod Gopalan and Alfred King-yin Lam *Pages 1-10 (10)

Abstract:


Background: The clinical pathological features, as well as the cellular mechanisms of miR-195, have not been investigated in thyroid carcinoma. Objective: The aim of this study is to identify the interactions of vascular endothelial growth factor (VEGF), p53 and miR-195 in thyroid carcinoma. The clinical and pathological features of miR-195 were also investigated. Method: The expression levels of miR-195 were identified in 123 primary thyroid carcinomas, 40 lymph nodes with metastatic papillary thyroid carcinomas and seven non-neoplastic thyroid tissues (controls) as well as two thyroid carcinoma cell lines, B-CPAP (from metastasizing human papillary thyroid carcinoma) and MB-1 (from anaplastic thyroid carcinoma), by the real-time polymerase chain reaction. Using Western blot and immunofluorescence, the effects of exogenous miR-195 on VEGF-A and p53 protein expression levels were examined. Then, cell cycle and apoptosis assays were performed to evaluate the roles of miR-195 in cell cycle progression and apoptosis. Results: The expression of miR-195 was downregulated in majority of the papillary thyroid carcinoma tissue as well as in cells. Introduction of exogenous miR-195 resulted in downregulation of VEGF-A and upregulation of p53 protein expressions. Upregulation of miR-195 in thyroid carcinoma cells resulted in cell cycle arrest. Moreover, we demonstrated that miR-195 inhibits cell cycle progression by induction of apoptosis in the thyroid carcinoma cells. Conclusion: Our findings showed for the first time that miR-195 acts as a tumour suppressor and regulates cell cycle progression and apoptosis by targeting VEGF-A and p53 in thyroid carcinoma. The current study exhibited that miR-195 might represent a potential therapeutic target for patients with thyroid carcinomas having aggressive clinical behaviour.

Keywords:

VEGF-A, p53, microRNA, miR-195, angiogenesis, thyroid carcinoma.

Affiliation:

Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland, Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland, Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland, Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland, Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland



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