Long noncoding RNA HULC regulates the NF‐κB pathway and represents a promising prognostic biomarker in liver cancer

Abstract

Background Long noncoding RNAs (lncRNAs) are involved in a diverse array of biological processes. While lncRNAs are commonly upregulated in hepatocellular carcinoma (HCC), the specific regulatory roles they play in this oncogenic context require further study and clarification. Although HULC (lncRNA highly upregulated in liver cancer) is involved in disease pathogenesis, its precise role in this context remains unclear. Methods Here, we have explored the mechanistic relevance of HULC expression by assessing its expression in patient samples. The importance of this lncRNA in the onset and progression of HCC was investigated through in vitro approaches including Western blotting, quantitative PCR, Transwell assays, electron microscopy, wound healing assays, and real‐time cell analysis (RTCA). Additionally, the in vivo functions of this lncRNA were assessed using an orthotopic HCC xenograft in nude mouse model system. Results HULC was identified as a lncRNA that is highly upregulated in human liver tumors. In vitro, HULC was able to promote HCC malignancy, although its excess overexpression also led robust autophagic induction, promoting the increased expression of autophagy‐associated genes including LC3 and Beclin‐1. At a mechanistic level, HULC was able to promote the phosphorylation of p65 and IkBkB thus enhancing autophagy by increasing LC3II levels in a manner dependent upon the NF‐κB pathway. HULC downregulation was also linked to impaired orthotopic HCC tumor growth in vivo. The link between HULC and autophagy may play a role in disease progression. Conclusions These results suggest that HULC is an oncogenic lncRNA, and may thus offer value as a prognostic biomarker and promoter of HCC development, in addition to being a potential therapeutic target in this cancer type.

Exploring the mechanism of LncRNA CASC15 affecting hepatocellular carcinoma through miRNA

“…[ 29 ] Liu et al indicated that lncRNA HULC could be served as a promising prognostic biomarker for HCC by its function in promoting HCC malignancy. [ 31 ] Another study identified the prognostic value of lncRNAs for HCC based on a small sample size of clinical samples. [ 8 , 32 , 33 ] Recent evidence has determined that BACE1-AS, [ 34 ] and LINC01093/MYLK-AS1 [ 35 ] exert prognostic value for HCC mainly by data mining based on bioinformatics tools.…”

“…Research methods D16366 [8] qRT-PCR, ROC, Kaplan-Meier, Cox regression analysis SNHG20 [24] qRT-PCR, Univariate and multivariate analysis, function-loss experiments DGCR5 [32] qRT-PCR, ROC, Kaplan-Meier, Cox regression analysis BANCR [25] qRT-PCR, Clinicopathologic analysis, Multivariate regression analysis, function-loss experiments AC099850 [26] TCGA datasets, function-loss experiments, geneset enrichment analysis, immune cell infiltration, immune checkpoint molecule analysis SNHG17 [27] qRT-PCR, RNA sequencing, gain-and loss-of-function studies HMMR-AS1 [28] GEO database, loss-of-function experiments in vitro and in vivo, dual luciferase report SNHG17 [30] qRT-PCR, Kaplan-Meier and log-rank analyses, Cox regression analysis, loss-of-function experiments BACE1-AS [34] TCGA mining DIO3OS [37] TCGA datasets, Kaplan-Meier, Cox regression analysis, Gene set enrichment analysis HCLNC1 [29] microarray study, In vitro cell proliferation assays and an in vivo xenotransplanted HCC tumor model CASC9 [33] RT-qPCR, Kaplan-Meier, Cox regression analysis, luciferase reporter assay LINC01093/MYLK-AS1 [35] GEO database and TCGA dataset, bioinformatic analysis, RT-qPCR INKA1-AS1 [36] TCGA and GTEx databases, Pan-cancer assay, survival analysis, immune analysis HULC [31] in vitro approaches, in vivo orthotopic HCC xenograft mouse model HCC = hepatocellular carcinoma, lncRNAs = Long noncoding RNAs.…”