scholarly journals Artesunate inhibits cell proliferation, migration, and invasion of thyroid cancer by regulating the PI3K/AKT/FKHR pathway

Author(s):  
Zhiwei Xu ◽  
Xiaojian Liu ◽  
Daoping Zhuang

This study characterized the effects of artesunate on thyroid cancer and partially identified its related molecular mechanism. We determined the effect of artesunate on the proliferation of thyroid cancer cells using the MTT assay, cell colony formation experiments, and western blotting, and used flow cytometry to detect the apoptosis of cancer cells. Using a wound-healing assay, Transwell chamber experiments, and western blotting, we determined the effect of artesunate on cancer cell migration. By co-cultivating artesunate with the PI3K agonist, 740Y-P, we also partially identified the molecular mechanism. Artesunate significantly inhibited the growth, proliferation, migration, and invasion of thyroid cancer cells, and promoted the apoptosis of cancer cells. Using co-cultivation with a PI3K agonist, we found that the inhibitory effect of artesunate on cancer cells was mainly due to suppressing the PI3K/AKT/FKHR signaling pathway. By inhibiting the PI3K/AKT/FKHR signaling pathway, artesunate induced apoptosis of thyroid cancer cells and inhibited their proliferation and migration.

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Yan Zhou ◽  
Shanshan Liu ◽  
Yan Luo ◽  
Meiying Zhang ◽  
Xueling Jiang ◽  
...  

Thyroid cancer is a common malignant tumour of the endocrine system and ranks ninth in cancer incidence worldwide. An extensive body of evidence has demonstrated that lncRNAs play a critical role in the progression of thyroid cancer. The lncRNA MAPKAPK5-AS1 has been reported to be abnormally expressed and to play a role in the development of various human cancers. However, MAPKAPK5-AS1’s potential role in thyroid cancer progression remains unknown. The objective of our study was to explore the role and mechanism of MAPKAPK5-AS1 in thyroid cancer cells and provide a potential target for its biological diagnosis and treatment. We transfected sh-MAPKAPK5-AS1 and sh-NC into BCPAP and TPC-1 cells for loss-of-function assays. Results of RT-qPCR analysis demonstrated that MAPKAPK5-AS1 was more highly expressed in thyroid cancer cells compared to normal cells. Functional assays demonstrated that interfering with the expression of MAPKAPK5-AS1 notably repressed proliferation and invasion and accelerated apoptosis of BCPAP and TPC-1 cells. Mechanistically, we found that miR-519e-5p was negatively regulated by MAPKAPK5-AS1 and that tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) was a target of miR-519e-5p. Additionally, rescue assays demonstrated that downregulation of MAPKAPK5-AS1 expression inhibited cell proliferation, migration, and invasion and promoted apoptosis by sponging miR-519e-5p, thereby increasing YWHAH expression. Ultimately, our study revealed that MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cells by targeting the miR-519e-5p/YWHAH axis, which provides novel insight into the development and progression of thyroid cancer.


2014 ◽  
Vol 99 (7) ◽  
pp. E1163-E1172 ◽  
Author(s):  
Wei Qiang ◽  
Yuan Zhao ◽  
Qi Yang ◽  
Wei Liu ◽  
Haixia Guan ◽  
...  

Context: ZIC1 has been reported to be overexpressed and plays an oncogenic role in some brain tumors, whereas it is inactivated by promoter hypermethylation and acts as a tumor suppressor in gastric and colorectal cancers. However, until now, its biological role in thyroid cancer remains totally unknown. Objectives: The aim of this study is to explore the biological functions and related molecular mechanism of ZIC1 in thyroid carcinogenesis. Setting and Design: Quantitative RT-PCR (qRT-PCR) was performed to evaluate mRNA expression of investigated genes. Methylation-specific PCR was used to analyze promoter methylation of the ZIC1 gene. The functions of ectopic ZIC1 expression in thyroid cancer cells were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays. Results: ZIC1 was frequently down-regulated by promoter hypermethylation in both primary thyroid cancer tissues and thyroid cancer cell lines. Moreover, our data showed that ZIC1 hypermethylation was significantly associated with lymph node metastasis in patients with papillary thyroid cancer. Notably, restoration of ZIC1 expression in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrest and apoptosis by blocking the activities of the phosphatidylinositol-3-kinase (PI3K)/Akt and RAS/RAF/MEK/ERK (MAPK) pathways, and enhancing FOXO3a transcriptional activity. Conclusions: Our data demonstrate that ZIC1 is frequently inactivated by promoter hypermethyaltion and functions as a tumor suppressor in thyroid cancer through modulating PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3a.


2018 ◽  
Vol 24 ◽  
pp. 661-670 ◽  
Author(s):  
Yue Zhang ◽  
Bin Sun ◽  
Zhi Huang ◽  
Dai-Wei Zhao ◽  
Qingfan Zeng

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