Ma, Chen, Wu, Li, Mei, Jing, Teng, Tu, Jiang, Wang, Chen, Wang, Wang, Wei, Liu, Yuan (2020) Long noncoding RNA SPRY4-IT1 promotes proliferation and metastasis of hepatocellular carcinoma via mediating TNF signaling pathway Journal of cellular physiology ()


Our previous studies have indicated that long noncoding RNA (lncRNA) SPRY4 intronic transcript 1 (SPRY4-IT1) was highly expressed in hepatocellular carcinoma (HCC). However, it still remained unclear how SPRY4-IT1 worked in tumorgenesis in HCC. In this study, we tested the overexpression of SPRY4-IT1 in HCC tissues and cells through a quantitative real-time polymerase chain reaction. Statistical analyses showed that the upregulation had an association with the tumor node metastasis stage, thrombin time, and alkaline phosphatase. Furthermore, SPRY4-IT1 could be involved in cell proliferation, metastasis, and the epithelial-to-mesenchymal transition (EMT) process in HCC in vitro and in vivo. RNA-sequencing and transcriptome analysis were carried out to explore the mechanism of SPRY4-IT1 in HCC. With SPRY4-IT1 being knocked down or overexpressed, the level of proteins in the tumor necrosis factor (TNF) signaling pathway changed. We detected the RNA binding protein heterogeneous nuclear ribonucleoprotein L (HNRNPL) as a SPRY4-IT1 interacting protein through RNA pull-down assay and liquid chromatography-mass spectrometry, then verified through RNA immunoprecipitation. Downregulation of HNRNPL induced the change of proteins observed on SPRY4-IT1 downregulation revealing the SPRY4-IT1: HNRNPL complex in the TNF signaling pathway and EMT process in HCC. In general, our experimental data and analysis demonstrated the role of SPRY4-IT1 in promoting progress and metastasis of HCC by the TNF signaling pathway. © 2020 Wiley Periodicals, Inc.