Matrix stiffness-sensitive long noncoding RNA NEAT1 seeded paraspeckles in cancer cells

Todorovski, Vanja; Fox, Archa; Choi, Yu Suk

doi:10.1091/mbc.e20-02-0097

Cited by 19 publications

(17 citation statements)

References 52 publications

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“…Over the last few years many new stressors that induce changes in paraspeckle abundance have been found, including mitochondrial stress, [ 37 ] hypoxia, [ 89 ] heat shock, [ 88 ] mechanical inputs and numerous additional stressors that trigger the integrated stress response. [ 91 ] In general, paraspeckles increase, and have a cytoprotective role in the face of these stressors. In this section we describe the mechanisms both upstream and downstream of paraspeckle changes in a variety of different cell stressors.…”

Section: Paraspeckle Abundance Typically Increases With Cellular Stress Linked To Cytoplasmic Stress Structuresmentioning

confidence: 99%

“…In this context, paraspeckles in cancer cells are sensitive to the stiffness of their culture substrate: paraspeckle induction is greater following culture of triple negative breast cancer cells on soft, versus, stiff substrate. [ 91 ] While the consequences of this mechano‐sensitive induction of paraspeckles are yet to be determined, it provides yet another example of how paraspeckles alter when cells experience changes in their environment.…”

Section: Paraspeckle Abundance Typically Increases With Cellular Stress Linked To Cytoplasmic Stress Structuresmentioning

confidence: 99%

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Paraspeckle nuclear condensates: Global sensors of cell stress?

McCluggage

Fox

2021

BioEssays

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Paraspeckles are nuclear condensates, or membranelees organelles, that are built on the long noncoding RNA, NEAT1, and have been linked to many diseases. Although originally described as constitutive structures, here, in reviewing this field, we develop the hypothesis that cells increase paraspeckle abundance as part of a general stress response, to aid pro-survival pathways. Paraspeckles increase in many scenarios: when cells transform from one state to another, become infected with viruses and bacteria, begin to degenerate, under inflammation, in aging, and in cancer. Cells increase paraspeckles by increasing transcription of NEAT1 and adjusting its RNA processing.These increases in NEAT1 are driven by numerous stress-sensing signaling pathways, including signaling to mitochondria and stress granules, revealing crosstalk between the cytoplasm and nucleoplasm in the stress response. Thus, paraspeckles are an important piece of the puzzle in cellular homeostasis, and could be considered RNAscaffolded nuclear equivalents of dynamic stress-induced structures that form in the cytoplasm. We speculate that, in general, cells rely on phase-separated paraspeckles to transiently tweak gene regulation in times of cellular flux.

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Section: Paraspeckle Abundance Typically Increases With Cellular Stress Linked To Cytoplasmic Stress Structuresmentioning

confidence: 99%

Section: Paraspeckle Abundance Typically Increases With Cellular Stress Linked To Cytoplasmic Stress Structuresmentioning

confidence: 99%

Paraspeckle nuclear condensates: Global sensors of cell stress?

McCluggage

Fox

2021

BioEssays

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“…NEAT1 and H19, with high scores in our network, have gained wide recognition in mechanobiology by previous study, which confirmed the reliability of our work. Remarkably, studies of NEAT1 or H19 were carried out under different force conditions in various cells, which indicated that these lncRNAs may be universal mechanoresponsive factors like our study aimed to define ( Hirose et al, 2014 ; Heo et al, 2015 ; Le et al, 2016 ; Li et al, 2017 , 2018 ; Izadpanahi et al, 2018 ; Wu et al, 2018 ; An et al, 2019 ; Wang S. et al, 2019 ; Zhang Y. et al, 2019 ; Huang et al, 2019 ; Todorovski et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

A Quartet Network Analysis Identifying Mechanically Responsive Long Noncoding RNAs in Bone Remodeling

Cai

et al. 2022

Front. Bioeng. Biotechnol.

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Mechanical force, being so ubiquitous that it is often taken for granted and overlooked, is now gaining the spotlight for reams of evidence corroborating their crucial roles in the living body. The bone, particularly, experiences manifold extraneous force like strain and compression, as well as intrinsic cues like fluid shear stress and physical properties of the microenvironment. Though sparkled in diversified background, long noncoding RNAs (lncRNAs) concerning the mechanotransduction process that bone undergoes are not yet detailed in a systematic way. Our principal goal in this research is to highlight the potential lncRNA-focused mechanical signaling systems which may be adapted by bone-related cells for biophysical environment response. Based on credible lists of force-sensitive mRNAs and miRNAs, we constructed a force-responsive competing endogenous RNA network for lncRNA identification. To elucidate the underlying mechanism, we then illustrated the possible crosstalk between lncRNAs and mRNAs as well as transcriptional factors and mapped lncRNAs to known signaling pathways involved in bone remodeling and mechanotransduction. Last, we developed combinative analysis between predicted and established lncRNAs, constructing a pathway–lncRNA network which suggests interactive relationships and new roles of known factors such as H19. In conclusion, our work provided a systematic quartet network analysis, uncovered candidate force-related lncRNAs, and highlighted both the upstream and downstream processes that are possibly involved. A new mode of bioinformatic analysis integrating sequencing data, literature retrieval, and computational algorithm was also introduced. Hopefully, our work would provide a moment of clarity against the multiplicity and complexity of the lncRNA world confronting mechanical input.

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“…The long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), also found to be mechanosensitive, leads to the formation of paraspeckles when introduced to increased matrix stiffness. Accordingly, Todorovski et al have suggested them as a potential candidate for mechanosensing in cancer migration (Todorovski et al, 2020). Similarly, other lncRNAs, H19 and HOX transcript antisense RNA (HOTAIR), also crucially modulate the ECM components (D'Angelo & Agostini, 2018).…”

Section: The Role Of Extracellular Matrix In Shaping Tumor Transcriptomementioning

confidence: 99%

Interplay within tumor microenvironment orchestrates neoplastic RNA metabolism and transcriptome diversity

et al. 2021

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The heterogeneous population of cancer cells within a tumor mass interacts intricately with the multifaceted aspects of the surrounding microenvironment. The reciprocal crosstalk between cancer cells and the tumor microenvironment (TME) shapes the cancer pathophysiome in a way that renders it uniquely suited for immune tolerance, angiogenesis, metastasis, and therapy resistance. This dynamic interaction involves a dramatic reconstruction of the transcriptomic landscape of tumors by altering the synthesis, modifications, stability, and processing of gene readouts. In this review, we categorically evaluate the influence of TME components, encompassing a myriad of resident and infiltrating cells, signaling molecules, extracellular vesicles, extracellular matrix, and blood vessels, in orchestrating the cancer-specific metabolism and diversity of both mRNA and noncoding RNA, including micro RNA, long noncoding RNA, circular RNA among others. We also highlight the transcriptomic adaptations in response to the physicochemical idiosyncrasies of TME, which include tumor hypoxia, extracellular acidosis, and osmotic stress. Finally, we provide a nuanced analysis of existing and prospective therapeutics targeting TME to ameliorate cancer-associated RNA metabolism, consequently thwarting the cancer progression.

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Matrix stiffness-sensitive long noncoding RNA NEAT1 seeded paraspeckles in cancer cells

Cited by 19 publications

References 52 publications

Paraspeckle nuclear condensates: Global sensors of cell stress?

Paraspeckle nuclear condensates: Global sensors of cell stress?

A Quartet Network Analysis Identifying Mechanically Responsive Long Noncoding RNAs in Bone Remodeling

Interplay within tumor microenvironment orchestrates neoplastic RNA metabolism and transcriptome diversity

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