Long noncoding RNA SPRY4‐IT1 promotes proliferation and metastasis of hepatocellular carcinoma via mediating TNF signaling pathway

Abstract

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.

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

“… 23 The long non-coding RNA (lncRNA) SPRY4-IT1 regulates tumor necrosis factor (TNF) signaling in mediating EMT in HCC. 24 The matrix metalloproteinases (MMPs) also participate in invasiveness of HCC cells, so that ADAM17 induces MMP-21 expression that is in favor of increasing HCC progression. 25 As mentioned, lncRNAs regulate HCC progression.…”

Identification of latent biomarkers in connection with progression and prognosis in oral cancer by comprehensive bioinformatics analysis

“…Mir-215-5p over expression reduces the migration and invasion of colorectal cancer cells through the interaction of extracellular matrix receptors [ 28 ]. SPRY4-IT1 promotes hepatocarcinogenesis and metastasis through TNF signaling pathway [ 29 ]. Microrna-27b inhibits tumor metastasis and adhesion by regulating the focal adhesion pathway [ 30 ].…”

NF-κB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay

“…Providing new insight into the role of SPRY4-IT1 in cancer was an important outcome of this study because its precise functions have been difficult to resolve, with reports of both tumorsuppressive and oncogenic activity. For example, SPRY4-IT1 is upregulated in many cancer types including breast cancer, cholangiocarcinoma [23], pancreatic ductal adenocarcinoma [24], hepatic cellular carcinoma [25,26], and melanoma [22]. In contrast, it appears to be downregulated in non-small-cell lung cancer [27] and gastric cancer [28] and acts as a potential tumor suppressor.…”