Long non-coding RNAs and genes contributing to the generation of cancer stem cells in hepatocellular carcinoma identified by RNA sequencing analysis

Cao, Liye; Zhang, Quan; Cheng, Shujie; Chen, Zhi; Hua, Zhijuan; Yang, Jihong; Liú, Dan; Cui, Na

doi:10.3892/or.2016.5120

Cited by 8 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed up‐regulation of lncRNAs, such as LINC00152, which has been implicated in the progression of gastric cancer and HCC . Similarly, down‐regulated LINC01018 may also contribute to hepatocellular carcinogenesis as epigenetic silencing of this lncRNA has been shown to promote HCC proliferation .…”

Section: Discussionmentioning

confidence: 53%

“…We also observed up-regulation of lncRNAs, such as LINC00152, which has been implicated in the progression of gastric cancer and HCC. (31,32) Similarly, down-regulated LINC01018 may also contribute to hepatocellular carcinogenesis as epigenetic silencing of this lncRNA has been shown to promote HCC proliferation. (33) Diminished LINC01093 has been associated with HCC progression, and this was the most deregulated lncRNA in our study, with a decreased fold change of 30.4.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Survey of Molecular Heterogeneity in Hepatocellular Carcinoma

Jovel

Lin

OʼKeefe

et al. 2018

Hepatology Communications

View full text Add to dashboard Cite

Understanding the heterogeneity of dysregulated pathways associated with the development of hepatocellular carcinoma (HCC) may provide prognostic and therapeutic avenues for disease management. As HCC involves a complex process of genetic and epigenetic modifications, we evaluated expression of both polyadenylated transcripts and microRNAs from HCC and liver samples derived from two cohorts of patients undergoing either partial hepatic resection or liver transplantation. Copy number variants were inferred from whole genome low‐pass sequencing data, and a set of 56 cancer‐related genes were screened using an oncology panel assay. HCC was associated with marked transcriptional deregulation of hundreds of protein‐coding genes. In the partially resected livers, diminished transcriptional activity was observed in genes associated with drug catabolism and increased expression in genes related to inflammatory responses and cell proliferation. Moreover, several long noncoding RNAs and microRNAs not previously linked with HCC were found to be deregulated. In liver transplant recipients, down‐regulation of genes involved in energy production and up‐regulation of genes associated with glycolysis were detected. Numerous copy number variants events were observed, with hotspots on chromosomes 1 and 17. Amplifications were more common than deletions and spanned regions containing genes potentially involved in tumorigenesis. Colony stimulating factor 1 receptor (CSF1R), fibroblast growth factor receptor 3 (FGFR3), fms‐like tyrosine kinase 3 (FLT3), nucleolar phosphoprotein B23 (NPM1), platelet‐derived growth factor receptor alpha polypeptide (PDGFRA), phosphatase and tensin homolog (PTEN), G‐protein‐coupled receptors‐like receptor Smoothened (SMO), and tumor protein P53 (TP53) were mutated in all tumors; another 26 cancer‐related genes were mutated with variable penetrance. Conclusion: Our results underscore the marked molecular heterogeneity between HCC tumors and reinforce the notion that precision medicine approaches are needed for management of individual HCC. These data will serve as a resource to generate hypotheses for further research to improve our understanding of HCC biology. (Hepatology Communications 2018; 00:000‐000)

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

A Survey of Molecular Heterogeneity in Hepatocellular Carcinoma

Jovel

Lin

OʼKeefe

et al. 2018

Hepatology Communications

View full text Add to dashboard Cite

show abstract

“…Deregulated genes also includes lncRNAs, like upregulation of LINC00152, which has been implicated in progression of gastric cancer and HCC [51][52][53][54], or downregulation of LINC01018 which, when epigenetically silenced, has been shown to promote HCC proliferation [55]. The top deregulated lncRNA in our study was LINC01093 (fold-change 30.4), which has been reported downregulated in association with HCC progression [56,57].…”

Section: Discussionmentioning

confidence: 71%

Novel insights into the molecular heterogeneity of hepatocellular carcinoma

Jovel

Lin

OʼKeefe

et al. 2017

Preprint

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is influenced by numerous factors, which results in diverse genetic, epigenetic and transcriptional scenarios, thus posing obvious challenges for disease management. We scrutinized the molecular heterogeneity of HCC with a multi-omics approach in two small cohorts of resected and explanted livers. Whole-genome transcriptomics was conducted, including polyadenylated transcripts and micro (mi)-RNAs. Copy number variants (CNV) were inferred from whole genome low-pass sequencing data. Fifty-six cancer-related genes were screened using an oncology panel assay. HCC was associated with a dramatic transcriptional deregulation of hundreds of protein-coding genes suggesting downregulation of drugs catabolism, induction of inflammatory responses, and increased cell proliferation in resected livers. Moreover, several long non-coding RNAs and miRNAs not reported previously in the context of HCC were found deregulated. In explanted livers, downregulation of genes involved in energy-producing processes and upregulation of genes aiding in glycolysis were detected. Numerous CNV events were observed, with conspicuous hotspots on chromosomes 1 and 17. Amplifications were more common than deletions, and spanned regions containing genes potentially involved in tumorigenesis. CSF1R, FGFR3, FLT3, NPM1, PDGFRA, PTEN, SMO and TP53 were mutated in all tumors, while other 26 cancer-related genes were mutated with variable penetrance. Our results highlight a remarkable molecular heterogeneity between HCC tumors and reinforce the notion that precision medicine approaches are urgently needed for cancer treatment. We expect that our results will serve as a valuable dataset that will generate hypotheses for us or other researchers to evaluate to ultimately improve our understanding of HCC biology.

show abstract

“…The role of lncRNAs as non-coding regulators of oncogenesis is well documented [34] , and they serve as key biomarkers and regulators of protein translation in a range of cancers [35] . When we assessed the relative expression and prognostic relevance of DE-lncRNAs in the GSE140845 dataset using the GEPIA and LncRNA2Target platforms, we identi ed 4 lncRNAs potentially related to patient outcomes [36] .…”

Section: Discussionmentioning

confidence: 99%

Construction of Novel mRNA-miRNA-lncRNA Regulatory Networks Associated with Prognosis of HCV Related HCC

Ma¹,

Shao

Shi

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Infection with hepatitis C virus (HCV) can cause hepatic fibrosis and cirrhosis, thereby significantly increasing the risk of HCC development. Many prior studies have shown that oncogenesis and cancer progression are governed by competing endogenous RNA (ceRNA) networks composed of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs. As such, we herein sought to identify and evaluate the prognostic relevance of novel ceRNA network related to HCC associated with HCV. Methods: Differentially expressed genes (DEGs) in the GSE140845 Gene Expression Omnibus (GEO) dataset were identified using NetworkAnalyst, and were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Gene, Genome (KEGG) pathway, and Reactome analyses. In addition, a protein-protein interaction (PPI) network was generated, and key hub genes were detected. Hub gene expression levels, as well as those of their upstream lncRNAs and miRNAs and associated survival analyses were conducted using appropriate bioinformatics databases. Predicted target relationships were additionally used to establish putative ceRNA networks for HCV-related HCC. Results: 372 and 360 upregulated and downregulated significant DEGs were identified, respectively. Functional enrichment analyses suggested that DE-mRNAs were associated with nuclear division, the cell cycle, and ATPase activity. The top 11 genes with the greatest degree of connectivity among these DE-mRNAs were selected for subsequent prognostic evaluation. The differential expression of six of these candidate mRNAs (BUB1, BUB1B, CDC20, CDC45, CDK1, NDC80) in liver tissue was validated. After further analyses of the expression and prognostic relevance of the miRNAs and lncRNAs predicted to lie upstream of these DE-mRNAs, we identified 22 miRNAs and 4 lncRNAs significantly associated with poorer-HCV-related HCC prognosis. By combining the results of these analyses, we also identified the BUB1-hsa-miR-193a-3p-MALAT1 ceRNA sub-network as being related to the survival of these patients. Conclusion: This study providing novel insights into the mRNA-miRNA-lncRNA ceRNA network and reveals potential lncRNA biomarkers in HCV related HCC.

show abstract

Long non-coding RNAs and genes contributing to the generation of cancer stem cells in hepatocellular carcinoma identified by RNA sequencing analysis

Cited by 8 publications

References 41 publications

A Survey of Molecular Heterogeneity in Hepatocellular Carcinoma

A Survey of Molecular Heterogeneity in Hepatocellular Carcinoma

Novel insights into the molecular heterogeneity of hepatocellular carcinoma

Construction of Novel mRNA-miRNA-lncRNA Regulatory Networks Associated with Prognosis of HCV Related HCC

Contact Info

Product

Resources

About