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Co-expression network analysis of lncRNAs and mRNAs in rat liver tissue reveals the complex interactions in response to pathogenic cytotoxicity.

ABSTRACT: Liver is one of the most vital organs to maintain homeostasis because of its peculiar detoxification functionalities to detoxify chemicals and metabolize drugs and toxins. Due to its crucial functions, the liver is also prone to various diseases, i.e., hepatitis, cirrhosis and hepatoma, etc. Additionally, long non-coding RNAs (lncRNAs) has emerged as key regulators which are found to play important roles in transcription, splicing, translation, replication, chromatin shaping and post translational modification of proteins in living cells. However, the underlying mechanisms of biological processes mediated by lncRNA remain unclear. Here, with the aim of disclosing potential lncRNAs implicated in the biological processes in liver in response to cytotoxicity, we performed a co-expression network analysis based on the transcriptome data of the damaged liver tissue of Rattus norvegicus induced by three cytotoxic compounds (carbon tetrachloride, chloroform and thioacetamide). Our analysis unveils that many biological processes and pathways were collectively affected by the three cytotoxic compounds, including drug metabolism, oxidation-reduction process, oxidative stress, glucuronidation, liver development and flavonoid biosynthetic process, etc. Also, our network analysis has identified several highly conserved lncRNA-mRNA interactions participating in those correlated processes and pathways, implying their potential roles in response to the induced cytotoxicity in liver. Our study provides new insights into lncRNA-mRNA regulatory mechanisms in response to pathogenic cytotoxic damaging in liver and facilitates the development of lncRNA-oriented therapies for hepatic diseases in the future.

SUBMITTER: Leng D

PROVIDER: S-EPMC6775316 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Co-expression network analysis of lncRNAs and mRNAs in rat liver tissue reveals the complex interactions in response to pathogenic cytotoxicity.

Leng Dongliang D Huang Chen C Lei Kuan Cheok KC Sun Shixue S Sun Baoqing B Zhang Xiaohua Douglas XD

International journal of biological sciences 20190822 11

Liver is one of the most vital organs to maintain homeostasis because of its peculiar detoxification functionalities to detoxify chemicals and metabolize drugs and toxins. Due to its crucial functions, the liver is also prone to various diseases, i.e., hepatitis, cirrhosis and hepatoma, etc. Additionally, long non-coding RNAs (lncRNAs) has emerged as key regulators which are found to play important roles in transcription, splicing, translation, replication, chromatin shaping and post translation ...[more]

PMID: 31595148

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Project description:Although studies provide insights into the neurobiology of stress and depression, the exact molecular mechanisms underlying their pathologies remain largely unknown. Long non-coding RNA (lncRNA) has been implicated in brain functions and behavior. A potential link between lncRNA and psychiatric disorders has been proposed. However, it remains undetermined whether IncRNA regulation, in the brain, contributes to stress or depression pathologies. In this study, we used a valid animal model of depression-like symptoms; namely learned helplessness, RNA-seq, Gene Ontology and co-expression network analyses to profile the expression pattern of lncRNA and mRNA in the hippocampus of mice. We identified 6346 differentially expressed transcripts. Among them, 340 lncRNAs and 3559 protein coding mRNAs were differentially expressed in helpless mice in comparison with control and/or non-helpless mice (inescapable stress resilient mice). Gene Ontology and pathway enrichment analyses indicated that induction of helplessness altered expression of mRNAs enriched in fundamental biological functions implicated in stress/depression neurobiology such as synaptic, metabolic, cell survival and proliferation, developmental and chromatin modification functions. To explore the possible regulatory roles of the altered lncRNAs, we constructed co-expression networks composed of the lncRNAs and mRNAs. Among our differentially expressed lncRNAs, 17% showed significant correlation with genes. Functional co-expression analysis linked the identified lncRNAs to several cellular mechanisms implicated in stress/depression neurobiology. Importantly, 57% of the identified regulatory lncRNAs significantly correlated with 18 different synapse-related functions. Thus, the current study identifies for the first time distinct groups of lncRNAs regulated by induction of learned helplessness in the mouse brain. Our results suggest that lncRNA-directed regulatory mechanisms might contribute to stress-induced pathologies; in particular, to inescapable stress-induced synaptic modifications.

Dataset Information

Co-expression network analysis of lncRNAs and mRNAs in rat liver tissue reveals the complex interactions in response to pathogenic cytotoxicity.

Publications

Co-expression network analysis of lncRNAs and mRNAs in rat liver tissue reveals the complex interactions in response to pathogenic cytotoxicity.

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