MicroRNA miR-378-3p is a novel regulator of endothelial autophagy and function

Bu, Shuhan; Joseph, Jameela; Nguyen, Hien; Ehsan, Mehroz; Rasheed, Berk; Singh, Aman; Qadura, Mohammad; Frisbee, Jefferson C.; Singh, Krishna K.

doi:10.1016/j.jmccpl.2022.100027

Cited by 7 publications

(13 citation statements)

References 50 publications

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“…We have previously reported that the loss of ATG7 in endothelial cells leads to impaired autophagy and EndMT in vitro and in vivo [7]. We next reported a reduced expression of PDIA-4 following pharmacologic inhibition of autophagy in endothelial cells [12]. In this study, we have shown that the loss of PDIA-4 is associated with autophagy inhibition, which is in line with the loss of ATG7-associated autophagic inhibition.…”

Section: Loss Of Pdia-4 Induced Endmt In Endothelial Cellssupporting

confidence: 81%

“…We previously reported that the loss of ATG7 in endothelial cells is associated with the inhibition of autophagy and the induction of EndMT in endothelial cells [7]. We then reported a reduced expression of PDIA-4 in endothelial cells following pharmacologic inhibition of autophagy [12]. We continued this line of investigation, and now we report that loss of PDIA-4 inhibits autophagy and induces EndMT.…”

Section: Discussionmentioning

confidence: 63%

“…Previously, the reduced expression of protein disulfide isomerase 4 (PDIA-4) was reported in endothelial cells following pharmacologic inhibition of autophagy [12]. Protein disulfide isomerases (PDIs) function as oxidoreductases and as chaperons that assist with the formation of disulfide bonds to help proteins fold into their final conformation [13].…”

Section: Introductionmentioning

confidence: 99%

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Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival

Bu,

Singh,

Nguyen

et al. 2024

IJMS

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Endothelial autophagy plays an important role in the regulation of endothelial function. The inhibition of endothelial autophagy is associated with the reduced expression of protein disulfide isomerase 4 (PDIA-4); however, its role in endothelial cells is not known. Here, we report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cell architecture, accompanied by the loss of endothelial markers and the gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). The loss of PDIA-4 activated TGFβ-signaling, and inhibition of TGFβ-signaling suppressed EndMT in PDIA-4- silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate endothelial function and/or limit autophagy and EndMT in (patho-)physiological conditions.

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Section: Loss Of Pdia-4 Induced Endmt In Endothelial Cellssupporting

confidence: 81%

Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

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Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival

Bu,

Singh,

Nguyen

et al. 2024

IJMS

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“…All cells continually engage in autophagy ("self-eating"), an essential process that encompasses the encapsulation of the cell's own macromolecules and organelles in the cytoplasm, followed by the lysosomal digestion of these biowastes into metabolic materials (e.g., amino acids, nucleic acids, phospholipids, etc.) [94,95]. Biowastes of autophagy include mRNAs, turnover proteins, toxic misfolded aggregates, desensitized receptors, and dysfunctional organelles such as abnormally proliferated mitochondria and peroxisomes.…”

Section: Dox Impairs Autophagymentioning

confidence: 99%

“…Autophagy in ECs strictly determines endothelial function and its metabolic implications. Indeed, loss of autophagy induces endothelial dysfunction; interestingly, agingassociated loss of autophagy closely correlates with loss of eNOS regulation and endothelial function [94]. As Dox impairs autophagy in various stages in cardiomyocytes, ECs likely incur similar damages, suggesting that Dox may also induce endothelial dysfunction through impairing endothelial autophagy.…”

Section: Dox-induced Endothelial Dysfunction Endotheliotoxicity and C...mentioning

confidence: 99%

Different Mechanisms in Doxorubicin-Induced Cardiomyopathy: Impact of BRCA1 and BRCA2 Mutations

Nguyen,

Frisbee,

Singh

2024

Hearts

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Germline mutations in Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) cause breast, ovarian, and other cancers, and the chemotherapeutic drug doxorubicin (Dox) is widely used to treat these cancers. However, Dox use is limited by the latent induction of severe cardiotoxicity known as Dox-induced cardiomyopathy, for which there are no specific treatments currently available. Dox is administered into the systemic circulation, where it readily translocates into sub-cellular compartments and disrupts the integrity of DNA. Accumulating evidence indicates that oxidative stress, DNA damage, inflammation, and apoptosis all play a central role in Dox-induced cardiomyopathy. The BRCA1 and BRCA2 proteins are distinct as they perform crucial yet separate roles in the homologous recombination repair of DNA double-strand breaks, thereby maintaining genomic integrity. Additionally, both BRCA1 and BRCA2 mitigate oxidative stress and apoptosis in both cardiomyocytes and endothelial cells. Accordingly, BRCA1 and BRCA2 are essential regulators of pathways that are central to the development of cardiomyopathy induced by Doxorubicin. Despite extensive investigations, there exists a gap in knowledge about the role of BRCA1 and BRCA2 in Doxorubicin-induced cardiomyopathy. Here, we review the previous findings and associations about the expected role and associated mechanisms of BRCA1 and 2 in Dox-induced cardiomyopathy and future perspectives.

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Evolving landscape of detection and targeting miRNA/epigenetics for therapeutic strategies in ovarian cancer

Dey Bhowmik,

Shaw,

Gopinatha Pillai

et al. 2025

Cancer Letters

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MicroRNA miR-378-3p is a novel regulator of endothelial autophagy and function

Cited by 7 publications

References 50 publications

Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival

Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival

Different Mechanisms in Doxorubicin-Induced Cardiomyopathy: Impact of BRCA1 and BRCA2 Mutations

Evolving landscape of detection and targeting miRNA/epigenetics for therapeutic strategies in ovarian cancer

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