Dataset Information

Comprehensive analysis of long non?coding RNA?messenger RNA?microRNA co?expression network identifies cell cycle?related lncRNA in hepatocellular carcinoma.

ABSTRACT: Long non?coding RNAs (lncRNAs) have been shown to contribute to progression and prognosis of hepatocellular carcinoma (HCC). However, expression profiling and interaction of lncRNAs with messenger RNAs (mRNAs) and microRNAs (miRNAs) remain largely unknown in HCC. The expression profiling of lncRNAs, mRNA and miRNAs was obtained using microarray. The Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to characterize potential functions of differentially expressed mRNAs. Cytoscape was applied to construct an lncRNA?miRNA?mRNA co?expression network and candidate lncRNAs were validated via quantitative PCR in 30 pairs of HCC and adjacent tumor?free tissues. In this study, 1,056 upregulated and 1,288 downregulated lncRNAs were identified, while 2,687 mRNAs and 6 miRNAs were aberrantly expressed in HCC compared with adjacent tumor?free tissues. Potential functions of differentially expressed mRNAs were demonstrated to significantly participate in modulating critical genes in the cell cycle, such as cyclin E1 and cyclin B2. After screening, 95 lncRNAs, 5 miRNAs and 36 mRNAs were recruited for construction of lncRNA?mRNA?miRNA co?expression network in the cell cycle pathway. Subsequently, the top 5 lncRNAs that potentially modulate critical genes in the cell cycle were selected as the candidates for further verification. Kaplan?Meier curves using the Cancer Genome Atlas database showed that 13 targeted mRNAs were associated with overall survival of HCC patients. Finally, three lncRNAs, including ENST00000522221, lnc?HACE1?6:1 and lnc?ICOSLG?11:1, are significantly upregulated in HCC tissues compared with adjacent tumor?free tissues. These findings suggest that lncRNAs play essential roles in the pathogenesis of HCC via regulating coding genes and miRNAs, and may be important targets for diagnosis and treatment of this disease.

SUBMITTER: Zhu HR

PROVIDER: S-EPMC6777664 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comprehensive analysis of long non‑coding RNA‑messenger RNA‑microRNA co‑expression network identifies cell cycle‑related lncRNA in hepatocellular carcinoma.

Zhu Hai-Rong HR Yu Xiang-Nan XN Zhang Guang-Cong GC Shi Xuan X Bilegsaikhan Enkhnaran E Guo Hong-Ying HY Liu Li-Li LL Cai Yu Y Song Guang-Qi GQ Liu Tao-Tao TT Dong Ling L Janssen Harry L A HLA Weng Shu-Qiang SQ Wu Jian J Shen Xi-Zhong XZ Zhu Ji-Min JM

International journal of molecular medicine 20190823 5

Long non‑coding RNAs (lncRNAs) have been shown to contribute to progression and prognosis of hepatocellular carcinoma (HCC). However, expression profiling and interaction of lncRNAs with messenger RNAs (mRNAs) and microRNAs (miRNAs) remain largely unknown in HCC. The expression profiling of lncRNAs, mRNA and miRNAs was obtained using microarray. The Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to characterize potential functions of differen ...[more]

PMID: 31485608

Similar Datasets

Project description:In the Americas, L. infantum (syn. chagasi) is the main cause of human visceral leishmaniasis. The role of neutrophils as part of the innate response to Leishmania spp. infection is dubious and varies according to the species causing the infection. Global expression of coding RNAs, microRNAs and long non-coding RNAs changes as part of the immune response against pathogens. Changes in mRNA and non-coding RNA expression resulting from infection by Leishmania spp. are widely studied in macrophages, but scarce in neutrophils, the first cell to encounter the trypanosomatid, especially following infection by L. infantum. Herein, we aimed to understand the expression patterns of coding and non-coding transcripts during acute in vitro infection of human neutrophils by L. infantum. We isolated neutrophils from whole blood of healthy male donors (n = 5) and split into groups: 1) infected with L. infantum (MOI = 5:1), and 2) uninfected controls. After 3 hours of exposure of infected group to promastigotes of L. infantum, followed by 17 hours of incubation, total RNA was extracted and total RNA-Seq and miRNA microarray were performed. A total of 212 genes were differentially expressed in neutrophils following RNA-Seq analysis (log2(FC)±0.58, FDR≤0.05). In vitro infection with L. infantum upregulated the expression of 197 and reduced the expression of 92 miRNAs in human neutrophils (FC±2, FDR≤0.01). Lastly, 5 downregulated genes were classified as lncRNA, and of the 10 upregulated genes, there was only 1 lncRNA. Further bioinformatic analysis indicated that changes in the transcriptome and microtranscriptome of neutrophils, following in vitro infection with L. infantum, may impair phagocytosis, apoptosis and decrease nitric oxide production. Our work sheds light on several mechanisms used by L. infantum to control neutrophil-mediated immune response and identifies several targets for future functional studies, aiming at the development of preventive or curative treatments for this prevalent zoonosis.

Project description:RNASEH1-AS1, a long non-coding RNA (lncRNA) divergently transcribed from the antisense strand of its neighboring protein-coding gene ribonuclease H1 (RNASEH1), has recently been demonstrated to be involved in tumor progression. However, the association between RNASEH1-AS1 and hepatocellular carcinoma (HCC) remains unclear. In the present study, first, the expression of RNASEH1-AS1 in HCC and its correlation with clinicopathological features, prognosis, diagnosis, immune cell infiltration of HCC patients was inspected using relevant R packages based on The Cancer Genome Atlas (TCGA) data. RNASEH1-AS1 was found to be up-regulated in most cancer types, including HCC, and its overexpression was significantly associated with histologic grade and AFP level as well as poor prognosis, and was an independent risk factor affecting overall survival with good diagnostic and prognostic values for HCC. RNASEH1-AS1 was inversely associated with the infiltration of most immune cell types, including plasmacytoid dendritic cells (pDC), B cells and neutrophils. Second, a total of 1109 positively co-expressed genes (PCEGs) of RNASEH1-AS1 were screened out in HCC by correlation analysis in batches (|Spearman's r| >0.4 and adjusted P value <0.01). GO and KEGG enrichment analysis indicated that PCEGs of RNASEH1-AS1 were mainly related to RNA processing, ribosome biogenesis, transcription and histone acetylation. The top 10 hub genes (EIF4A3, WDR43, WDR12, DKC1, NAT10, UTP18, DDX18, BYSL, DDX10, PDCD11) were identified by constructing the protein-protein interaction (PPI) network, and they were all highly expressed in HCC and positively correlated with histological grade. Third, a risk model was constructed based on four RNASEH1-AS1-related hub genes (EIF4A3, WDR12, DKC1, and NAT10) with good prognostic predictive potential via univariate Cox and the least absolute selection operator (LASSO) regression analysis. Fourth, experimental validation revealed that RNASEH1-AS1 was significantly elevated in HCC tissues and several cell lines, and its knockdown could suppress the proliferation, migration, and invasion of HCC cells. Finally, mechanistic studies demonstrated that the stability of RNASEH1-AS1 could be regulated by DKC1 via their direct interaction. Taken together, RNASEH1-AS1 may serve as a potential prognostic and diagnostic biomarker and oncogenic lncRNA for HCC.

Dataset Information

Comprehensive analysis of long non?coding RNA?messenger RNA?microRNA co?expression network identifies cell cycle?related lncRNA in hepatocellular carcinoma.

Publications

Comprehensive analysis of long non‑coding RNA‑messenger RNA‑microRNA co‑expression network identifies cell cycle‑related lncRNA in hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets