Regulation of impulsive and aggressive behaviours by a novel lncRNA

Labonté, Benoit; Abdallah, Khaled; Maussion, Gilles; Yerko, Volodymyr; Yang, Jennie; Bittar, Thibault P.; Quessy, Francis; Golden, Sam A.; Navarro, Luis; Checknita, Dave; Gigek, Carolina Oliveira; López, Juan Pablo; Neve, Rachael L.; Russo, Scott J.; Tremblay, Richard E.; Côté, Gilles; Meaney, Michael J.; Mechawar, Naguib; Nestler, Eric J.; Turecki, Gustavo

doi:10.1038/s41380-019-0637-4

Cited by 28 publications

(18 citation statements)

References 68 publications

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“…Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are over 200 nucleotides in length, which have no protein-coding function but have epigenetic regulation and other biological functions ( Peng et al, 2017 ). Currently, mounting evidences have demonstrated that lncRNAs and mRNAs played critical roles in various physiological processes, such as cell activity, gene regulation, and so on ( Fukushima and Kida, 2019 ; De Troyer et al, 2020 ; Labonté et al, 2020 ). Therefore, dissecting how lncRNAs regulate tumor progress attracts great interest from researchers ( Majidinia and Yousefi, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of Key lncRNA–mRNA Pairs and Functional lncRNAs in Breast Cancer by Integrative Analysis of TCGA Data

Zheng

Chen

et al. 2021

Front. Genet.

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Long non-coding RNAs (lncRNAs) play an important role in many diseases and are involved in the post-transcriptional regulatory network of tumors. The purpose of this study is to mine new lncRNA–mRNA regulatory pairs and analyze the new mechanism of lncRNA involvement in breast cancer progression. Using breast cancer miRNA and mRNA expression profiling from The Cancer Genome Atlas (TCGA), we identified 59 differentially expressed lncRNAs, 88 differentially expressed miRNAs, and 1,465 differentially expressed mRNAs between breast cancer tissue and adjacent normal breast cancer. Whereafter, four candidate lncRNAs (FGF14-AS2, LINC01235, AC055854.1, and AC124798.1) were identified by the Kaplan–Meier (K–M) plotter. Furthermore, we screened the hub lncRNA (LINC01235) through univariate Cox analysis, multivariate Cox analysis, and qPCR validation, which was significantly correlated with breast cancer stage, ER status, and pathological N. Subsequently, 107 LINC01235-related mRNAs were obtained by combining differentially expressed miRNAs, differentially expressed mRNAs, and LINC01235 targeting miRNAs and mRNAs. The protein–protein interaction (PPI) network was established by Cytoscape software, and 53 key genes were screened. Function and pathway enrichment showed that LINC01235-related key genes might be involved in the process of cell differentiation, cell proliferation, and p53 signal pathway. In addition, LINC01235 has been confirmed to regulate the proliferation, migration, and invasion of MCF-7 cells in in vitro experiments. Furthermore, we screened three mRNAs (ESR1, ADRA2A, and DTL) associated with breast cancer drug resistance from key genes. Through RNA interference experiments in vitro and correlation analysis, we found that there was a negative feedback mechanism between LINC01235 and ESR1/ADRA2A. In conclusion, our results suggest that LINC01235-ESR1 and LINC01235-ADRA2A could serve as important co-expression pairs in the progression of breast cancer, and LINC01235 plays a key role as an independent prognostic factor in patients with breast cancer. The findings of this work greatly increase our understanding of the molecular regulatory mechanisms of lncRNA in breast cancer.

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Section: Introductionmentioning

confidence: 99%

Identification of Key lncRNA–mRNA Pairs and Functional lncRNAs in Breast Cancer by Integrative Analysis of TCGA Data

Zheng

Chen

et al. 2021

Front. Genet.

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“…Since chronically isolated mice have altered behaviors toward other individuals, such as increased aggression but also blunted response to social novelty (Zelikowsky et al, 2018), it is possible that lncRNAs are important modulators of behavioral responses due to chronic social isolation in mammals. Consistently, aggressive behaviors have also been associated with changes in lncRNAs expression (Punzi et al, 2019;Labonté et al, 2020). The monoamine oxidase A (MAOA) associated ncRNA (MAALIN) is a lncRNA located in the 3 intergenic region separating the tail-to-tail oriented MAO genes A and B.…”

Section: Lncrnasmentioning

confidence: 94%

“…Although different lines of evidence suggest that ncRNAs are transcriptionally altered in the brain of rodents after social isolation, direct and functional evidence on their contribution to behavioral and physiological consequences of prolonged social isolation is still sparse (Verma et al, 2018;Antony et al, 2020;Chang et al, 2020). However miRNAs and lncRNAs were proven to modulate social behaviors which are also altered as the result of prolonged social isolation (Haramati et al, 2011;Dias et al, 2014;Issler et al, 2014;Jin et al, 2016;Zhu et al, 2017;Cheng et al, 2018;Lackinger et al, 2019;Labonté et al, 2020;Ma et al, 2020).…”

Section: Non-coding Rnas Are Major Regulators Of Social Behaviormentioning

confidence: 99%

“…The monoamine oxidase A (MAOA) associated ncRNA (MAALIN) is a lncRNA located in the 3 intergenic region separating the tail-to-tail oriented MAO genes A and B. In humans, the promoter of MAALIN is hypomethylated in neurons of the DG from suicidal subjects with a history of impulsive aggressive disorders and this correlates with lower expression of MAOA gene, which has been implicated in aggressive disorders both in humans and animals (Labonté et al, 2020). Overexpression of MAALIN in the hippocampus of aggressive mice induces a discrete downregulation of MAOA and results in a trend for increased duration of attacks toward other mice, suggesting that MAALIN could affect aggressive behavior (Labonté et al, 2020), a stereotypic behavioral response for male mice exposed to chronic social isolation.…”

Section: Lncrnasmentioning

confidence: 99%

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Long-Term Impact of Social Isolation and Molecular Underpinnings

Arzate-Mejía

Lottenbach²,

Schindler³

et al. 2020

Front. Genet.

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Prolonged periods of social isolation can have detrimental effects on the physiology and behavior of exposed individuals in humans and animal models. This involves complex molecular mechanisms across tissues in the body which remain partly identified. This review discusses the biology of social isolation and describes the acute and lasting effects of prolonged periods of social isolation with a focus on the molecular events leading to behavioral alterations. We highlight the role of epigenetic mechanisms and non-coding RNA in the control of gene expression as a response to social isolation, and the consequences for behavior. Considering the use of strict quarantine during epidemics, like currently with COVID-19, we provide a cautionary tale on the indiscriminate implementation of such form of social isolation and its potential damaging and lasting effects in mental health.

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“…Of interest, a recent finding from our group indicates that individuals who died by suicide present differential methylation in the promoter region of a locus that codes for MAALIN, a long non-coding RNA. This transcript, which is lowly abundant and primarily expressed in the nucleus, is increased in individuals who died by suicide, negatively regulates the expression of MAOA, and increases latency to attack, a measure of impulsive-aggressive behavior in animals ( Labonté et al, 2020 ).…”

Section: Molecular Impacts Of Camentioning

confidence: 99%

Molecular impacts of childhood abuse on the human brain

Ibrahim

Almeida

Nagy

et al. 2021

Neurobiology of Stress

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Childhood abuse (CA) is a prevalent global health concern, increasing the risk of negative mental health outcomes later in life. In the literature, CA is commonly defined as physical, sexual, and emotional abuse, as well as neglect. Several mental disorders have been associated with CA, including depression, bipolar disorder, schizophrenia, and post-traumatic stress disorder, along with an increased risk of suicide. It is thought that traumatic life events occurring during childhood and adolescence may have a significant impact on essential brain functions, which may persist throughout adulthood. The interaction between the brain and the external environment can be mediated by epigenetic alterations in gene expression, and there is a growing body of evidence to show that such changes occur as a function of CA. Disruptions in the HPA axis, myelination, plasticity, and signaling have been identified in individuals with a history of CA. Understanding the molecular impact of CA on the brain is essential for the development of treatment and prevention measures. In this review, we will summarize studies that highlight the molecular changes associated with CA in the human brain, along with supporting evidence from peripheral studies and animal models. We will also discuss some of the limitations surrounding the study of CA and propose extracellular vesicles as a promising future approach in the field.

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Regulation of impulsive and aggressive behaviours by a novel lncRNA

Cited by 28 publications

References 68 publications

Identification of Key lncRNA–mRNA Pairs and Functional lncRNAs in Breast Cancer by Integrative Analysis of TCGA Data

Identification of Key lncRNA–mRNA Pairs and Functional lncRNAs in Breast Cancer by Integrative Analysis of TCGA Data

Long-Term Impact of Social Isolation and Molecular Underpinnings

Molecular impacts of childhood abuse on the human brain

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