The effects of mitochondria-associated long noncoding RNAs in cancer mitochondria: New players in an old arena

Zhao, Yijing; Sun, Lemeng; Wang, Rachel R.; Hu, Ji-Fan; Cui, Jiuwei

doi:10.1016/j.critrevonc.2018.08.005

Cited by 52 publications

(53 citation statements)

References 61 publications

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“…ncRNAs involved in the epigenetic regulation of mitochondrial gene expression can be encoded by both the nuclear and mitochondrial genomes, however, it is not clear whether the mtDNA encoded ncRNAs are derived from mitochondrial genes integrated into the nuclear genome (i.e., NUMTs) or are actually transcribed inside the mitochondria (reviewed in Vendramin et al, 2017). DOI 10.1002/em andCorey, 2017;Sas-Chen et al, 2017;Olavarria et al, 2018;Zhao et al, 2018). DOI 10.1002/em andCorey, 2017;Sas-Chen et al, 2017;Olavarria et al, 2018;Zhao et al, 2018).…”

Section: Mitochondrial Gene Regulation By Noncoding Rnasmentioning

confidence: 99%

“…The levels of ncRNAs can be altered manipulating cellular and mitochondrial functions during various types of cancer making them a potential target for cancer therapy (reviewed in Bienertova-Vasku et al, 2013; Matsui Environmental andMolecular Mutagenesis. DOI 10.1002/em andCorey, 2017;Sas-Chen et al, 2017;Olavarria et al, 2018;Zhao et al, 2018).…”

Section: Mitochondrial Gene Regulation By Noncoding Rnasmentioning

confidence: 99%

“…Similar to mRNA, they can also undergo post-transcriptional modifications such as alternative splicing, 5 0 end capping, and 3 0 polyadenylation (reviewed in Mercer and Mattick, 2013). Several lncRNA encoded by the mitochondrial genome have been identified and participate in the regulation of mitochondrial gene expression or act as retrograde signaling molecules to maintain activity of nuclear genes (reviewed in Dong et al, 2017;Zhao et al, 2018). The first three mtDNA encoded lncRNA identified were a mitochondrial sense ncRNA (SncmtRNA) and two antisense ncRNAs (ASncmtRNAs-1 and -2), and they contain sense and antisense strands of 16s rRNA gene, respectively, connected to a 5 0 leader fragment derived from respective complementary strands.…”

Section: Long Noncoding Rnasmentioning

confidence: 99%

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Mitochondrial DNA: Epigenetics and environment

Sharma

Pasala

Prakash

2019

Environ and Mol Mutagen

120

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Maintenance of the mitochondrial genome is essential for proper cellular function. For this purpose, mitochondrial DNA (mtDNA) needs to be faithfully replicated, transcribed, translated, and repaired in the face of constant onslaught from endogenous and environmental agents. Although only 13 polypeptides are encoded within mtDNA, the mitochondrial proteome comprises over 1500 proteins that are encoded by nuclear genes and translocated to the mitochondria for the purpose of maintaining mitochondrial function. Regulation of mtDNA and mitochondrial proteins by epigenetic changes and post‐translational modifications facilitate crosstalk between the nucleus and the mitochondria and ultimately lead to the maintenance of cellular health and homeostasis. DNA methyl transferases have been identified in the mitochondria implicating that methylation occurs within this organelle; however, the extent to which mtDNA is methylated has been debated for many years. Mechanisms of demethylation within this organelle have also been postulated, but the exact mechanisms and their outcomes is still an active area of research. Mitochondrial dysfunction in the form of altered gene expression and ATP production, resulting from epigenetic changes, can lead to various conditions including aging‐related neurodegenerative disorders, altered metabolism, changes in circadian rhythm, and cancer. Here, we provide an overview of the epigenetic regulation of mtDNA via methylation, long and short noncoding RNAs, and post‐translational modifications of nucleoid proteins (as mitochondria lack histones). We also highlight the influence of xenobiotics such as airborne environmental pollutants, contamination from heavy metals, and therapeutic drugs on mtDNA methylation. Environ. Mol. Mutagen., 60:668–682, 2019. © 2019 Wiley Periodicals, Inc.

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Section: Mitochondrial Gene Regulation By Noncoding Rnasmentioning

confidence: 99%

Section: Mitochondrial Gene Regulation By Noncoding Rnasmentioning

confidence: 99%

Section: Long Noncoding Rnasmentioning

confidence: 99%

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Mitochondrial DNA: Epigenetics and environment

Sharma

Pasala

Prakash

2019

Environ and Mol Mutagen

120

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“…Interestingly in both the KEGG pathways DE lncRNA sets were enriched within the lumen of Mitochondria whereas non-progressive class-wise testing showed no such shreds of evidence. Concrete evidence for many mitochondria-associated lncRNAs in the regulation of mitochondrial bioenergetics and cross-talk with nuclei has already existed in literature [38]. Also, during the cellular hypoxia mitochondria is the first organelle to be reprogrammed..…”

Section: Discussionmentioning

confidence: 99%

“…What is more interesting to see is that both pathways have DE lncRNA sets enriched within the lumen of Mitochondria whereas non-progressive showed no such shreds of evidence of mitochondria. Concrete evidence for many mitochondria-associated lncRNAs in the regulation of mitochondrial bioenergetics and cross-talk with nuclei has already existed in literature 37 . Our experimental design also enriched NEAT1 as an upregulated gene in the antigen-stimulated set of progressive samples.…”

Section: Discussionmentioning

confidence: 99%

lncRNA Mediated Hijacking of T-cell Hypoxia Response Pathway byMycobacterium tuberculosisPredicts Latent to Active Progression in Humans

Mehra

Kumar

Srivastava

et al. 2020

Preprint

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Cytosolic functions of Long non-coding RNAs including mRNA translation masking and sponging are major regulators of biological pathways. Formation of T cell-bounded hypoxic granuloma is a host immune defense for containing infected Mtb-macrophages. Our study exploits the mechanistic pathway of Mtb-induced HIF1A silencing by the antisense lncRNA-HIF1A-AS2 in T cells. Computational analysis of in-vitro T-cell stimulation assays in progressors(n=119) versus latent(n=221) tuberculosis patients revealed the role of lncRNA mediated disruption of hypoxia adaptation pathways in progressors.We found 291 upregulated and 227 downregulated lncRNAs that were correlated at mRNA level with HIF1A and HILPDA which are major players in hypoxia response. We also report novel lncRNA-AC010655 (AC010655.4 and AC010655.2) in cis with HILPDA, both of which contain binding sites for the BARX2 transcription factor, thus indicating a mechanistic role. Detailed comparison of infection with antigenic stimulation showed a non-random enrichment of lncRNAs in the cytoplasmic fraction of the cell in progressors. The lack of this pattern in non-progressors indicates the hijacking of the lncRNA dynamics by Mtb. The in-vitro manifestation of this response in the absence of granuloma indicates pre-programmed host-pathogen interaction between T-cells and Mtb regulated through lncRNAs, thus tipping this balance towards progression or containment of Mtb. Finally, we trained multiple machine learning classifiers for reliable prediction of latent to the active progression of patients, yielding a model to guide aggressive treatment.

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Long non‐coding RNAs and microorganism‐associated cancers

Ranjbar

Behjatfar

Teimouri

et al. 2021

Cell Biochemistry & Function

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Cancerous cells are abnormal cells characterized by aberrant growth and proliferation, which can involve various types of cells and tissues. Through numerous signalling pathways, many mechanisms are involved in cells that keep them normal. These signalling pathways are tightly set by different proteins whose expression is regulated by a large number of factors. In other words, when a regulating factor does not act properly or undergoes a change in its function or expression, the result will be that the subordinate gene and subsequently the related protein will show deranged expression and activity. This leads to disordered signalling pathways which bring about uncontrolled proliferation in cells. One of the most significant factors in adjusting the expression of genes is noncoding RNAs. It should be noted that all underlying causes initiating malignancy try to alter the main regulatory factors in cellular processes and gene expression and direct the cell to an unregulated state.Microorganisms have been identified as one of the important elements to direct normal cells to abnormality. That is, they probably agitate the malignant traits through manipulating significant factors such as ncRNAs in given cells using their own or host-related factors. The present study is aimed at examining how the long noncoding RNAs are involved in microorganism-mediated cancers.

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The effects of mitochondria-associated long noncoding RNAs in cancer mitochondria: New players in an old arena

Cited by 52 publications

References 61 publications

Mitochondrial DNA: Epigenetics and environment

Mitochondrial DNA: Epigenetics and environment

lncRNA Mediated Hijacking of T-cell Hypoxia Response Pathway byMycobacterium tuberculosisPredicts Latent to Active Progression in Humans

Long non‐coding RNAs and microorganism‐associated cancers

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