MicroRNA-222 Promotes Invasion and Metastasis of Papillary Thyroid Cancer Through Targeting Protein Phosphatase 2 Regulatory Subunit B Alpha Expression

• Published in: Thyroid (New York, N.Y.) Vol. 28; no. 9; p. 1162
• Main Authors: Huang, Yanrui, Yu, Shuang, Cao, Siting, Yin, Yali, Hong, Shubin, Guan, Hongyu, Li, Yanbing, Xiao, Haipeng
• Format: Journal Article
• Language: English
• Published: United States 01.09.2018
• Subjects: Adult; Cell Line, Tumor; Cell Movement - physiology; Female; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; Protein Phosphatase 2 - genetics; Protein Phosphatase 2 - metabolism; Thyroid Cancer, Papillary - genetics; Thyroid Cancer, Papillary - metabolism; Thyroid Cancer, Papillary - pathology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; AKT; PPP2R2A; invasion; papillary thyroid carcinoma; metastasis; miR-222
• ISSN: 1557-9077
• DOI: 10.1089/thy.2017.0665

Increasing evidence indicates that microRNA dysfunction is involved in the pathogenesis and progression of cancer. MicroRNA-222 (miR-222) is upregulated in papillary thyroid carcinoma (PTC). However, the role of miR-222 in invasion and metastasis of PTC remains unknown. This study investigated the function of miR-222 and its underlying mechanism in the progression of PTC. The expression of miR-222 was detected by quantitative reverse transcription polymerase chain reaction, and its correlation with various clinical characteristics was analyzed. The role of miR-222 in PTC cell migration ability was assessed with Transwell assays and wound-healing assays in both TPC-1 and K1 cells. By using bioinformatics analyses and dual-luciferase 3'-UTR reporter assays, the study identified the direct target of miR-222 and the downstream pathways of PTC. Further, the study confirmed the role of miR-222 in promoting PTC distant metastasis in vivo by injecting TPC-1 cells into nude mice. This study confirmed that miR-222 was upregulated in PTC tissues compared to adjacent thyroid tissues and that it correlated with aggressive cancer phenotypes. The results indicate that ectopic miR-222 enhanced cell migration and invasion of thyroid cancer cells in vitro and distant pulmonary metastases in vivo. Protein phosphatase 2 regulatory subunit B alpha (PPP2R2A), a tumor suppressor, was identified as a direct target of miR-222 through the 3'-UTR of PPP2R2A. Restoring PPP2R2A expression led to the attenuation of migration and invasion in miR-222-overexpressing thyroid cancer cells. Moreover, we found that miR-222 promoted invasion and metastasis partly through the AKT signaling pathway. Taken together, the results suggest that miR-222 promotes tumor invasion and metastasis in thyroid cancer by targeting PPP2R2A. Thus, miR-222 could serve as a potential diagnostic biomarker, as well as an attractive therapeutic tool for thyroid cancer.