Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland, Australia.
Dental Research Centre, Research Centre for Molecular Medicine, Oral Pathology Department, Dental Faculty, Hamadan University of Medical Sciences, Hamadan, Iran.
Curr Cancer Drug Targets. 2019;19(7):561-570. doi: 10.2174/1568009618666180628154727.
The clinical pathological features, as well as the cellular mechanisms of miR-195, have not been investigated in thyroid carcinoma.
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.
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.
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.
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.
miR-195 在甲状腺癌中的临床病理特征和细胞机制尚未得到研究。
本研究旨在鉴定血管内皮生长因子 (VEGF)、p53 和 miR-195 在甲状腺癌中的相互作用。还研究了 miR-195 的临床和病理特征。
通过实时聚合酶链反应，在 123 例原发性甲状腺癌、40 例有转移性甲状腺乳头状癌的淋巴结和 7 例非肿瘤性甲状腺组织（对照）以及 2 种甲状腺癌细胞系 B-CPAP（来自转移性甲状腺乳头状癌）和 MB-1（来自间变性甲状腺癌）中鉴定 miR-195 的表达水平。通过 Western blot 和免疫荧光，检查外源性 miR-195 对 VEGF-A 和 p53 蛋白表达水平的影响。然后，进行细胞周期和凋亡测定，以评估 miR-195 在细胞周期进展和凋亡中的作用。
miR-195 的表达在大多数甲状腺乳头状癌组织和细胞中下调。引入外源性 miR-195 导致 VEGF-A 下调和 p53 蛋白表达上调。甲状腺癌细胞中 miR-195 的上调导致细胞周期停滞。此外，我们证明 miR-195 通过诱导甲状腺癌细胞凋亡来抑制细胞周期进展。
我们的研究结果首次表明，miR-195 作为一种肿瘤抑制因子，通过靶向甲状腺癌中的 VEGF-A 和 p53 调节细胞周期进展和凋亡。目前的研究表明，miR-195 可能成为具有侵袭性临床行为的甲状腺癌患者的潜在治疗靶点。
