A long noncoding RNA,LncMyoD, modulates chromatin accessibility to regulate muscle stem cell myogenic lineage progression

Epigenetics regulation plays a critical role in determining cell identity by controlling the accessibility of lineage-specific regulatory regions. In muscle stem cells, epigenetic mechanisms of how chromatin accessibility is modulated during cell fate determination are not fully understood. Here, we identified a long noncoding RNA,LncMyoD, that functions as a chromatin modulator for myogenic lineage determination and progression. The depletion ofLncMyoDin muscle stem cells led to the down-regulation of myogenic genes and defects in myogenic differentiation.LncMyoDexclusively binds with MyoD and not with other myogenic regulatory factors and promotes transactivation of target genes. The mechanistic study revealed that loss ofLncMyoDprevents the establishment of a permissive chromatin environment at myogenic E-box–containing regions, therefore restricting the binding of MyoD. Furthermore, the depletion ofLncMyoDstrongly impairs the reprogramming of fibroblasts into the myogenic lineage. Taken together, our study shows thatLncMyoDassociates with MyoD and promotes myogenic gene expression through modulating MyoD accessibility to chromatin, thereby regulating myogenic lineage determination and progression.

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Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells

eLife ◽

10.7554/elife.54782 ◽

2021 ◽

Vol 10 ◽

Author(s):

Andrea Cipriano ◽

Martina Macino ◽

Giulia Buonaiuto ◽

Tiziana Santini ◽

Beatrice Biferali ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Epigenetic Regulation ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Muscle Stem Cells ◽

Cis Acting ◽

Adult Muscle ◽

Histone Lysine Methyltransferase ◽

Muscle Genes

Skeletal muscle possesses an outstanding capacity to regenerate upon injury due to the adult muscle stem cell (MuSC) activity. This ability requires the proper balance between MuSC expansion and differentiation, which is critical for muscle homeostasis and contributes, if deregulated, to muscle diseases. Here, we functionally characterize a novel chromatin-associated long noncoding RNA (lncRNA), Lnc-Rewind, which is expressed in murine MuSCs and conserved in human. We find that, in mouse, Lnc-Rewind acts as an epigenetic regulator of MuSC proliferation and expansion by influencing the expression of skeletal muscle genes and several components of the WNT (Wingless-INT) signalling pathway. Among them, we identified the nearby Wnt7b gene as a direct Lnc-Rewind target. We show that Lnc-Rewind interacts with the G9a histone lysine methyltransferase and mediates the in cis repression of Wnt7b by H3K9me2 deposition. Overall, these findings provide novel insights into the epigenetic regulation of adult muscle stem cells fate by lncRNAs.

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XIST: A Meaningful Long Noncoding RNA in NSCLC Process

Current Pharmaceutical Design ◽

10.2174/1381612826999201202102413 ◽

2020 ◽

Vol 26 ◽

Author(s):

Yujie Shen ◽

Yexiang Lin ◽

Kai Liu ◽

Jinlan Chen ◽

Juanjuan Zhong ◽

...

Keyword(s):

Therapeutic Target ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Critical Role ◽

Biological Functions ◽

Potential Therapeutic Target ◽

Considerable Evidence ◽

Lncrna Xist ◽

Nsclc Patients ◽

The Relationship

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.

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Empowering Muscle Stem Cells for the Treatment of Duchenne Muscular Dystrophy

Cells Tissues Organs ◽

10.1159/000514305 ◽

2021 ◽

pp. 1-14

Author(s):

Romina L. Filippelli ◽

Natasha C. Chang

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Cell Function ◽

Critical Role ◽

Membrane Integrity ◽

Muscle Membrane ◽

Muscle Stem Cell ◽

Muscle Stem Cells

Duchenne muscular dystrophy (DMD) is a devastating and debilitating muscle degenerative disease affecting 1 in every 3,500 male births worldwide. DMD is progressive and fatal; accumulated weakening of the muscle tissue leads to an inability to walk and eventual loss of life due to respiratory and cardiac failure. Importantly, there remains no effective cure for DMD. DMD is caused by defective expression of the <i>DMD</i> gene, which encodes for dystrophin, a component of the dystrophin glycoprotein complex. In muscle fibers, this protein complex plays a critical role in maintaining muscle membrane integrity. Emerging studies have shown that muscle stem cells, which are adult stem cells responsible for muscle repair, are also affected in DMD. DMD muscle stem cells do not function as healthy muscle stem cells, and their impairment contributes to disease progression. Deficiencies in muscle stem cell function include impaired establishment of cell polarity leading to defective asymmetric stem cell division, reduced myogenic commitment, impaired differentiation, altered metabolism, and enhanced entry into senescence. Altogether, these findings indicate that DMD muscle stem cells are dysfunctional and have impaired regenerative potential. Although recent advances in adeno-associated vector and antisense oligonucleotide-mediated mechanisms for gene therapy have shown clinical promise, the current therapeutic strategies for muscular dystrophy do not effectively target muscle stem cells and do not address the deficiencies in muscle stem cell function. Here, we discuss the merits of restoring endogenous muscle stem cell function in degenerating muscle as a viable regenerative medicine strategy to mitigate DMD.

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Nanomedicine Directs Neuronal Differentiation of Neural Stem Cells via Silencing Long Noncoding RNA for Stroke Therapy

Nano Letters ◽

10.1021/acs.nanolett.0c04560 ◽

2021 ◽

Author(s):

Bingling Lin ◽

Liejing Lu ◽

Yong Wang ◽

Qinyuan Zhang ◽

Zhe Wang ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Neuronal Differentiation ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Stroke Therapy

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Determining Long Noncoding RNA Mechanisms in Stem Cells using Automated Image Analysis and Single Molecule RNA-Fluorescent in Situ Hybridization

Biophysical Journal ◽

10.1016/j.bpj.2020.11.1024 ◽

2021 ◽

Vol 120 (3) ◽

pp. 136a

Author(s):

Benjamin Kesler ◽

Gregor Neuert

Keyword(s):

Stem Cells ◽

Image Analysis ◽

In Situ Hybridization ◽

Single Molecule ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Fluorescent In Situ Hybridization ◽

Automated Image Analysis

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KDM6A mediated expression of the long noncoding RNA DINO causes TP53 tumor suppressor stabilization in Human Papillomavirus type 16 E7 expressing cells

10.1101/2020.01.01.892612 ◽

2020 ◽

Author(s):

Surendra Sharma ◽

Karl Munger

Keyword(s):

Cell Death ◽

Tumor Suppressor ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Critical Role ◽

Metabolic Stress ◽

Dominant Negative ◽

Missing Link ◽

Hpv16 E6 ◽

E6 And E7

ABSTRACTHPV16 E7 has long been noted to stabilize the TP53 tumor suppressor. However, the molecular mechanism of TP53 stabilization by HPV16 E7 has remained obscure and can occur independent of E2F regulated MDM2 inhibitor, p14ARF. Here, we report that the Damage Induced Noncoding (DINO) lncRNA (DINOL) is the missing link between HPV16 E7 and increased TP53 levels. DINO levels are decreased in cells where TP53 is inactivated, either by HPV16 E6, expression of a dominant negative TP53 minigene or by TP53 depletion. DINO levels are increased in HPV16 E7 expressing cells. HPV16 E7 causes increased DINO expression independent of RB1 degradation and E2F1 activation. Similar to the adjacent CDKN1A locus, DINO expression is regulated by the histone demethylase, KDM6A. DINO stabilizes TP53 in HPV16 E7 expressing cells and as a TP53 transcriptional target, DINO levels further increase. Similar to other oncogenes such as adenovirus E1A or MYC, HPV16 E7 expressing cells are sensitized to cell death under conditions of metabolic stress and in the case of E7, this has been linked to TP53 activation. Consistent with earlier studies, we show that HPV16 E7 expressing keratinocytes are highly sensitive to metabolic stress induced by the antidiabetic drug, metformin. Metformin sensitivity of HPV16 E7 expressing cells is rescued by DINO depletion. This work identifies DINO as a critical mediator TP53 stabilization and activation in HPV16 E7 expressing cells.IMPORTANCEViral oncoproteins, including HPV16 E6 and E7 have been instrumental in elucidating the activities of cellular signaling networks including those governed by the TP53 tumor suppressor. Our study demonstrates that the long noncoding RNA DINO is the long sought missing link between HPV16 E7 and elevated TP53 levels. Importantly, the TP53 stabilizing DINO plays a critical role in the predisposition of HPV16 E7 expressing cells to cell death under metabolic stress conditions from metformin treatment.

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