Down regulated lncRNA MEG3 eliminates mycobacteria in macrophages via autophagy

Pawar, Kamlesh; Hanisch, Carlos; Vera, Sergio Eliseo Palma; Einspanier, Ralf; Sharbati, Soroush

doi:10.1038/srep19416

Cited by 113 publications

(105 citation statements)

References 71 publications

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“…Similarly, on the 1 st day of infection majority of the lncRNAs were upregulated on susceptible line relative to two other genetic lines. The expression number of DE’s correlated with the gradient of bacterial load between the three genetic lines: S > C > R. Previous report also indicated correlation of lncRNAs expression with microbial load44. Figure 4 shows abundance of selected hierarchically clustered lncRNAs among genetic lines after infection with Fp .…”

Section: Resultsmentioning

confidence: 72%

Differential expression of long non-coding RNAs in three genetic lines of rainbow trout in response to infection with Flavobacterium psychrophilum

Paneru

Al-Tobasei

Palti

et al. 2016

Sci Rep

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Bacterial cold-water disease caused by Flavobacterium psychrophilum is one of the major causes of mortality of salmonids. Three genetic lines of rainbow trout designated as ARS-Fp-R (resistant), ARS-Fp-C (control) and ARS-Fp-S (susceptible) have significant differences in survival rate following F. psychrophilum infection. Previous study identified transcriptome differences of immune-relevant protein-coding genes at basal and post infection levels among these genetic lines. Using RNA-Seq approach, we quantified differentially expressed (DE) long non-coding RNAs (lncRNAs) in response to F. psychrophilum challenge in these genetic lines. Pairwise comparison between genetic lines and different infection statuses identified 556 DE lncRNAs. A positive correlation existed between the number of the differentially regulated lncRNAs and that of the protein-coding genes. Several lncRNAs showed strong positive and negative expression correlation with their overlapped, neighboring and distant immune related protein-coding genes including complement components, cytokines, chemokines and several signaling molecules involved in immunity. The correlated expressions and genome-wide co-localization suggested that some lncRNAs may be involved in regulating immune-relevant protein-coding genes. This study provides the first evidence of lncRNA-mediated regulation of the anti-bacterial immune response in a commercially important aquaculture species and will likely help developing new genetic markers for rainbow trout disease resistance.

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Section: Resultsmentioning

confidence: 72%

Differential expression of long non-coding RNAs in three genetic lines of rainbow trout in response to infection with Flavobacterium psychrophilum

Paneru

Al-Tobasei

Palti

et al. 2016

Sci Rep

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“…reported that lncRNA-CD244 acted as an epigenetic regulator of IFN-γ and TNF-α production in CD8 + T cells and that it impacts CD8 + T cell immunity against active Mtb infection31. LncRNA-MEG3, which is shown to be a tumour suppressor gene, was downregulated in macrophages with BCG infection, leading to the induction of autophagy and enhanced eradication of intracellular pathogens32. In this study, we revealed that many lncRNAs were differentially expressed in macrophages with H37Ra or H37Rv infection, which indicated that lncRNAs might play an important role in the macrophages response to Mtb infection.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of long noncoding RNA and mRNA expression profiles in human macrophages infected with Mycobacterium tuberculosis

Yang

Wang

et al. 2016

Sci Rep

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Macrophages play a crucial role in the control and elimination of invading Mycobacterium tuberculosis (Mtb), and also serve as the major residence for Mtb. However, the interaction between macrophages and Mtb remains to be clearly determined. Although long noncoding RNAs (lncRNAs) have emerged as key regulators in many biological processes, their roles in anti-mycobacterial responses of macrophages remain to be elucidated. Here, we applied microarray analysis to examine lncRNA and mRNA expression profiles in human primary macrophages after 72 h of infection with H37Ra or H37Rv. Our results revealed that many lncRNAs were differentially expressed in macrophages after H37Ra or H37Rv infection, indicating a possible role for lncRNAs in immune responses induced by Mtb infection and providing important cues for further functional studies. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis of the differentially expressed mRNAs showed the potential functions and pathways related to the pathogenesis of Mtb infection. Finally, two lncRNAs, MIR3945HG V1 and MIR3945HG V2, were identified as novel candidate diagnostic markers for tuberculosis. Our results provide novel insight into the mechanisms of the pivotal Mtb-macrophage interactions, and reveal potential targets for diagnostics and the treatment of tuberculosis.

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“…Furthermore, knockdown of MEG3 resulted in the induction of autophagy, which helped to combat the intracellular BCG infection. Upon treatment with IFN-γ, increased autophagy led to sustained and significant MEG3 downregulation, reinforcing the effective eradication of mycobacteria (14). These investigations have identified a significant relationship between lncRNA and cell autophagy.…”

Section: Introductionmentioning

confidence: 95%

Long non-coding RNAs act as regulators of cell autophagy in diseases

Xu¹,

Yan²,

Qian³

et al. 2017

Oncology Reports

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Identification of long non-coding RNAs (lncRNAs) has provided a substantial increase in our understanding of the non-coding transcriptome. Studies have revealed a crucial function of lncRNAs in the modulation of cell autophagy in vitro and in vivo, further contributing to the hallmarks of disease phenotypes. These findings have profoundly altered our understanding of disease pathobiology, and may lead to the emergence of new biological concepts underlying autophagy-associated diseases, such as the carcinomas. Studies on the molecular mechanism of the lncRNA-autophagy axis may offer additional avenues for therapeutic intervention and biomarker assessment. In this review, we discuss recent findings on the multiple molecular roles of regulatory lncRNAs in the signaling pathways of cell autophagy. The emerging knowledge in this rapidly advancing field will offer novel insights into human diseases, especially cancers.

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Down regulated lncRNA MEG3 eliminates mycobacteria in macrophages via autophagy

Cited by 113 publications

References 71 publications

Differential expression of long non-coding RNAs in three genetic lines of rainbow trout in response to infection with Flavobacterium psychrophilum

Differential expression of long non-coding RNAs in three genetic lines of rainbow trout in response to infection with Flavobacterium psychrophilum

Microarray analysis of long noncoding RNA and mRNA expression profiles in human macrophages infected with Mycobacterium tuberculosis

Long non-coding RNAs act as regulators of cell autophagy in diseases

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