Light Chain Amyloidosis–Induced Autophagy Is Mediated by the Foxo3a/Beclin-1 Pathway in Cardiomyocytes

Zhang, Yuan; Yu, Wanpeng; Chang, Wenguang; Wang, Man; Zhang, Lei; Yu, F. Richard

doi:10.1016/j.labinv.2022.100001

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…Additionally, circular RNA ubiquitin protein ligase E3 component N-recognin 4 (circ-UBR4), circRNA E3 ubiquitin-protein ligase (circ-CHFR) and circRNA ubiquitin-specific peptidase 36 (circ_USP36) were shown to be upregulated in ox-LDL-induced human VSMCs. Circ-UBR4 sponges miR-637 and reduces the expression of miR-637, thereby promoting FOXO4 production ( 75 , 76 ). Similarly, circ-UBR4 also promotes human VSMC proliferation by sponging miR-107, miR-491-5p and miR-185-5p and then increasing the expression of ROCK1, NRP2 and FRS2 ( 77 – 79 ).…”

Section: Crosstalk Between Ubiquitin Ligases and Ncrnas Drives Vascul...mentioning

confidence: 99%

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

You,

Wen,

Tian

et al. 2024

Front. Immunol.

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Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin–proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers’ attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies.

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Section: Crosstalk Between Ubiquitin Ligases and Ncrnas Drives Vascul...mentioning

confidence: 99%

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

You,

Wen,

Tian

et al. 2024

Front. Immunol.

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“…Information on the general steps leading LCs to misfold and aggregate has been obtained from in vitro studies [11][12][13][14][15][16][17][18] . Experiments conducted in cardiomyocytes and cardiac fibroblasts provided advances in the mechanism of LC toxicity, showing that soluble oligomers and amyloidogenic deposits are both key players 14,[19][20][21][22] . While soluble oligomers reduce cell viability through aberrant interactions with critical cellular components and generation of radical oxygen species (ROS), resulting in mitochondria damage, the amyloid burden can contribute to organ damage by mechanical constraint and alteration of the tissue architecture 1 .…”

Section: Introductionmentioning

confidence: 99%

Modeling immunoglobulin light chain amyloidosis inCaenorhabditis elegans

Romeo,

Barzago,

Corbelli

et al. 2024

Preprint

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Cardiac involvement determines the survival of patients with immunoglobulin light chain (AL) amyloidosis, a rare systemic disease caused by the misfolding and deposition of monoclonal light chains (LCs). The reasons underlining their cardiac tropism remain unknown, and an animal model recapitulating the main pathological features of AL amyloidosis is instrumental. Taking advantage of the similarities between the vertebrate heart andC. elegans’ pharynx, we developed a new transgenic nematode expressing a human amyloidogenic λ LC whose sequence was deduced from an AL-affected patient with cardiac involvement (MNH). Strains expressing a non-amyloidogenic LC (MNM) or the empty vector only (MNV) were generated as controls. At variance with controls, LCs expressed in the body-wall muscle of MNH worms formed native soluble dimeric assemblies, which were secreted and reached different organs, including the pharynx. Noteworthy, MNH worms exerted a pharyngeal impairment resembling the bradycardia occurring in AL-affected patients, accompanied by increased radical oxygen species production and tissue ultrastructural damage. This new animal model can allow the elucidation of the mechanisms underlying the cardiac-specific tropism occurring in AL amyloidosis, providing innovative insights into the pathophysiology.Summary StatementWe generated a newC. elegansanimal model of cardiac AL amyloidosis. This model represents a uniquein vivotool for studying the cardiac-specific damage occurring in the disease.

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“…Based on their structural features, ncRNAs are further categorized into microRNA (miRNA) (13), long non-coding RNA (lncRNA) (14), circular RNA (circRNA) (15), small interfering RNA (16), and PIWI-interacting RNA (17). They participate in the regulation of various biological processes, including transcription, development, and immunity, by altering specific gene expression (18)(19)(20). Therefore, their dysregulation is closely correlated with various diseases, such as brain disease, diabetes, and cancer (21)(22)(23)(24)(25)(26)(27) NcRNA dysregulation has been reported to contribute to almost all aspects of LC development, including apoptosis, cell cycle, metastasis, and autophagy, as well as cell stemness (28-31).…”

Section: Introductionmentioning

confidence: 99%

Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications

Liu,

Ding,

Wang

et al. 2023

Front. Oncol.

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Lung cancer (LC) is a heterogeneous disease with high malignant degree, rapid growth, and early metastasis. The clinical outcomes of LC patients are generally poor due to the insufficient elucidation of pathological mechanisms, low efficiency of detection and assessment methods, and lack of individualized therapeutic strategies. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA), are endogenous regulators that are widely involved in the modulation of almost all aspects of life activities, from organogenesis and aging to immunity and cancer. They commonly play vital roles in various biological processes by regulating gene expression via their interactions with DNA, RNA, or protein. An increasing amount of studies have demonstrated that ncRNAs are closely correlated with the initiation and development of LC. Their dysregulation promotes the progression of LC via distinct mechanisms, such as influencing protein activity, activating oncogenic signaling pathways, or altering specific gene expression. Furthermore, some ncRNAs present certain clinical values as biomarker candidates and therapeutic targets for LC patients. A complete understanding of their mechanisms in LC progression may be highly beneficial to developing ncRNA-based therapeutics for LC patients. This review mainly focuses on the intricate mechanisms of miRNA, lncRNA, and circRNA involved in LC progression and discuss their underlying applications in LC treatment.

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Light Chain Amyloidosis–Induced Autophagy Is Mediated by the Foxo3a/Beclin-1 Pathway in Cardiomyocytes

Cited by 6 publications

References 21 publications

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

Modeling immunoglobulin light chain amyloidosis inCaenorhabditis elegans

Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications

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