Long Noncoding RNA Highly Upregulated in Liver Cancer Regulates the Tumor Necrosis Factor-α-Induced Apoptosis in Human Vascular Endothelial Cells

Abstract

Atherosclerosis is the major cause of myocardial infarction and stroke, which is a leading cause of morbidity and mortality in developed countries. During the pathological process of atherosclerosis, inflammation participates in all stages of atherosclerosis. Tumor necrosis factor-α (TNF-α), one of the most important inflammatory factor, induces apoptosis of endothelial cells, which play a central role in endothelial dysfunction. However, the underlying mechanism involved in long noncoding RNA (lncRNA) remains unclear. In the present study, we demonstrated the role of lncRNA highly upregulated in liver cancer (HULC) in TNF-α-induced apoptosis. HULC expression was decreased with TNF-α treatment. Restoring HULC expression rescued the apoptosis induced by TNF-α. HULC regulated TNF-α-induced apoptosis through regulation of miR-9 expression. Furthermore, RNA immunoprecipitation and RNA pull-down assays showed that HULC modulated miR-9 expression through association with DNA methyltransferases and suppression of miR-9 expression. HULC-miR-9 pathway may be a potential target for treating atherosclerosis.

LncRNA‐RP11‐714G18.1 suppresses vascular cell migration via directly targeting LRP2BP

“…Several recent studies have revealed that lncRNAs exert their biological functions partly through in trans or in cis modulation of the expression of nearby protein‐coding genes, providing an additional layer of modulation in molecular regulation . We therefore examined expression of LRP2BP in RP11‐714G18.1 overexpressing HUVECs and HA‐VSMCs.…”

“…Several recent studies have revealed that lncRNAs exert their biological functions partly through in trans or in cis modulation of the expression of nearby protein-coding genes, providing an additional layer of modulation in molecular regulation. 7,8,18,19 We therefore examined expression of LRP2BP in RP11-714G18.1 overexpressing HUVECs and HA-VSMCs. As shown in Figure 2b and c, both mRNA and protein levels of LRP2BP were significantly enhanced by lentivirus-mediated overexpression of RP11-714G18.1 in either HA-VSMCs or HUVECs, suggesting that the expression of LRP2BP can be upregulated by RP11-714G18.1.…”

Pro-Angiogenic Role of LncRNA HULC in Microvascular Endothelial Cells via Sequestrating miR-124

“…It has been well-accepted that lncRNA function to the regulation of gene expression via acting as endogenous sponges for various miRNAs [12,23]. LncRNA HULC could posttranscriptionally sponge miR-186 [24], miR-122 [8], miR-372/miR-373 [25], and miR-9 [26], preventing target genes from degradation by these miRNAs, and thereby participating in a wide range of cellular process, like cell proliferation, differentiation, migration, invasion, apoptosis and inflammatory response. Herein, we found that lncRNA HULC was a molecular sponge for miR-124, that lncRNA HULC sequestrated miR-124, preventing MCL-1 from binding with miR-124.…”

Long non-coding RNA HULC as a potential prognostic biomarker in human cancers: a meta-analysis

“…It is highly expressed in hepatocellular carcinoma and colorectal cancer with liver metastasis [14]. Since HULC expression has been shown during cancer growth and metastasis, it is a promising prognostic biomarker candidate for human cancers [15]. In recent years, HULC has been found to be dysregulated in osteosarcoma, pancreatic cancer, colorectal cancer, hepatocellular carcinoma, gastric cancer, hepatocellular carcinoma and large B-cell lymphoma [16–22].…”