miR-215 suppresses papillary thyroid cancer proliferation, migration, and invasion through the AKT/GSK-3β/Snail signaling by targeting ARFGEF1.

Abstract

The incidence of papillary thyroid cancer (PTC) has been rapidly increasing in recent years. PTC is prone to lymph node metastasization, which further increases the recurrence rate and mortality of thyroid cancer. However, the underlying mechanisms of this process remain elusive. Several reports have shown that the microRNA miR-215 plays an important role in cancer metastasis. Here, we investigated, for the first time, the potential association between miR-215 and metastasis in PTC. The results of qPCR analysis demonstrated that miR-215 was downregulated in PTC cell lines and tissues, and lower levels of miR-215 correlated with lymph node metastasis of PTC. In vitro and in vivo assays revealed that restoration of miR-215 dramatically inhibited PTC cell proliferation and metastasis. We identified ADP ribosylation factor guanine nucleotide-exchange factor 1 (ARFGEF1) as the target, which mediated the function of miR-215. The expression of ARFGEF1 was inhibited by miR-215, and the effects of miR-215 were abrogated by re-expression of ARFGEF1. Moreover, we found that miR-215 suppressed PTC metastasis by modulating the epithelial-mesenchymal transition via the AKT/GSK-3β/Snail signaling. In summary, our study proves that miR-215 inhibits PTC proliferation and metastasis by targeting ARFGEF1 and indicates miR-215 as a biomarker for PTC prognosis.

• Authors: Jihua Han, Meiyin Zhang, Chunlei Nie, Jinliang Jia, Fengyue Wang, Jiawei Yu, Wen Bi, Bo Liu, Ruinan Sheng, Guoqing He, Lingyu Kong, Lingling Zheng, Rui Pang, Zhaoming Ding, Lili Chen, Qiang Guan, Shangha Pan, Xianzhi Meng, Jin Xu, Lianxin Liu, Jiewu Zhang
• Journal: Cell death & disease (Cell Death Dis) Vol. 10 Issue 3 Pg. 195 (02 27 2019) ISSN: 2041-4889 [Electronic] England
• PMID: 30814512 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ARFGEF1 protein, human
• Guanine Nucleotide Exchange Factors
• MIRN215 microRNA, human
• MicroRNAs
• SNAI2 protein, human
• Snail Family Transcription Factors
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease Models, Animal
• Down-Regulation (genetics)
• Epithelial Cells (cytology, metabolism)
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Regulation, Neoplastic
• Glycogen Synthase Kinase 3 beta (genetics, metabolism)
• Guanine Nucleotide Exchange Factors (antagonists & inhibitors, genetics, metabolism)
• Humans
• Lymphatic Metastasis (genetics)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Neoplasm Recurrence, Local
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction (genetics)
• Snail Family Transcription Factors (genetics, metabolism)
• Thyroid Cancer, Papillary (genetics, metabolism, secondary)
• Thyroid Neoplasms (genetics, metabolism, pathology)
• Transplantation, Heterologous