Long noncoding RNA H19 is a critical oncogenic driver and contributes to epithelial-mesenchymal transition in papillary thyroid carcinoma

Abstract

Wei-Quan Liang,1,* De Zeng,2,* Chun-Fa Chen,1 Shu-Ming Sun,1 Xiao-Feng Lu,1 Chun-yan Peng,3 Hao-Yu Lin1 1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515000, People’s Republic of China; 2Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, People’s Republic of China; 3Department of Clinical Laboratory, Taihe Hospital of Hubei University of Medicine, Hubei 442008, People’s Republic of China *These authors contributed equally to this work Background: Growing evidence has indicated that the long noncoding RNA H19 (lncRNA H19), frequently deregulated in almost all tumor types tested, acted as a pivotal contributor to both cancer initiation and progression. However, the role of lncRNA H19 in human papillary thyroid carcinoma (PTC) remains controversial. The aim of the study was to investigate the expression and potential function of lncRNA H19 in human PTC.Patients and methods: The lncRNA H19 level was determined by quantitative real-time (RT)-PCR analyses in 58 PTC tissue samples and their paired paracancerous tissue samples. RNA interference, RT-PCR analysis, and Western blot assay were used to determine the impact of lncRNA H19 on epithelial-mesenchymal transition (EMT) markers in human PTC cells. The migratory and invasive capacities of PTC cells were determined by wound-healing and transwell migration and invasion assays.Results: lncRNA H19 expression was 2.417-fold higher in PTC tissues than their paired paracancerous tissue (95% CI: 1.898–2.935, P<0.0001). Higher level of lncRNA H19 was correlated to elevated expression of Vimentin, ZEB2, Twist, and Snail2. Inhibition of lncRNA H19 resulted in upregulation of E-cadherin and downregulation of Vimentin both at mRNA and protein levels. Conversely, enforced expression of the exogenous lncRNA H19 led to E-cadherin mRNA and protein downregulation and relative upregulation of Vimentin. Moreover, wound-healing and transwell migration and invasion assays showed that lncRNA H19 could promote the migratory and invasive abilities of PTC cells.Conclusion: The level of lncRNA H19 was significantly higher in PTC tissues than paired paracancerous tissue or normal tissues. Overexpression of lncRNA H19 was correlated with higher tumor burden of PTC. It also contributes to EMT process, as well as promotes migration and invasion of PTC cells. Keywords: long noncoding RNA H19 (lncRNA H19), papillary thyroid carcinoma, epithelial-mesenchymal transition  

Keywords

• long noncoding RNA H19 (lncRNA H19)
• papillary thyroid carcinoma
• epithelial-mesenchymal transition