HDAC4 Knockdown Induces Preeclampsia Cell Autophagy and Apoptosis by miR-29b

Du, Juan; Ji, Qinghong; Dong, Lihua; Meng, Yanping; Xin, Gang

doi:10.1007/s43032-020-00286-4

Cited by 20 publications

(14 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides binding to its molecular targets, digoxin was also found to mediate its antitumor activity by induction of apoptosis and autophagy [ 36 , 42 , 43 , 44 , 45 ], for which both histone deacetylases (HDACs) and inhibitor of apoptosis (IAP) have been proposed as important targets [ 46 , 47 , 48 ]. There are three classes with more than 10 members in the human HDAC family, with the similarity of the members in the same class being higher than that in different classes; the structures of these proteins are notably similar ( Figure S8 ).…”

Section: Resultsmentioning

confidence: 99%

“…These observations could have resulted from the different molecular modeling methodologies used, but nonetheless indicate that digoxigenin ( 10 ) may inhibit NKA by direct action or through a signaling transduction mechanism. In addition, both HDAC and PI3K regulate tumor proliferation, autophagy, and metabolism [ 46 , 49 , 50 ]; and the antitumor activity of the cardiac glycoside, cerberin, has been reported to be mediated through the PI3K/Akt/mTOR signaling pathway [ 52 ]. Thus, the present results suggest that digoxin ( 2 ) and its aglycone 10 mediate their antitumor activity through different mechanisms of action.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase and Other Targets for the Inhibition of Cancer Cell Proliferation

Ren

Burdette

et al. 2021

Molecules

View full text Add to dashboard Cite

Digoxin is a cardiac glycoside long used to treat congestive heart failure and found recently to show antitumor potential. The hydroxy groups connected at the C-12, C-14, and C-3′a positions; the C-17 unsaturated lactone unit; the conformation of the steroid core; and the C-3 saccharide moiety have been demonstrated as being important for digoxin’s cytotoxicity and interactions with Na+/K+-ATPase. The docking profiles for digoxin and several derivatives and Na+/K+-ATPase were investigated; an additional small Asn130 side pocket was revealed, which could be useful in the design of novel digoxin-like antitumor agents. In addition, the docking scores for digoxin and its derivatives were found to correlate with their cytotoxicity, indicating a potential use of these values in the prediction of the cancer cell cytotoxicity of other cardiac glycosides. Moreover, in these docking studies, digoxin was found to bind to FIH-1 and NF-κB but not HDAC, IAP, and PI3K, suggesting that this cardiac glycoside directly targets FIH-1, Na+/K+-ATPase, and NF-κB to mediate its antitumor potential. Differentially, digoxigenin, the aglycon of digoxin, binds to HDAC and PI3K, but not FIH-1, IAP, Na+/K+-ATPase, and NF-κB, indicating that this compound may target tumor autophagy and metabolism to mediate its antitumor propensity.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase and Other Targets for the Inhibition of Cancer Cell Proliferation

Ren

Burdette

et al. 2021

Molecules

View full text Add to dashboard Cite

show abstract

“…Previously, HDAC4 was demonstrated to be targeted by miR‐29b to participate in the modulation of decidua‐derived mesenchymal stem cells, thereby influencing the pathogenesis of PE (Xin et al, 2017). Furthermore, in PE, the aberrantly expressed HDAC4 can also be counteracted by miR‐29b, and HDAC4 knockdown triggers the autophagy and apoptosis of placental trophoblast cells (Du et al, 2021). In this study, depletion of HDAC4 was also discovered to repress the viability and facilitate the apoptosis of hESCs, alleviating the dysfunction of hESCs.…”

Section: Discussionmentioning

confidence: 99%

LncRNA MALAT1 promotes decidualization of endometrial stromal cells via sponging miR‐498‐3p and targeting histone deacetylase 4

Shi

Zhu

et al. 2022

Cell Biology International

View full text Add to dashboard Cite

Decidualization of human endometrial stromal cells (hESCs) is important for the maintenance of a successful pregnancy. Histone deacetylase 4 (HDAC4) was reported to be involved in the dysfunction of decidua-derived mesenchymal stem cells.However, the role of HDAC4 underlying decidualization of hESCs remains unclear.We intended to explore the function and molecular mechanism of HDAC4 in hESCs.In vitro expansion of hESCs using a serum-free medium was used to confirm the characteristics of hESCs. Gene expression in hESCs was evaluated by reverse transcription-quantitative polymerase chain reaction. CCK-8 assay, TUNEL staining, flow cytometry analysis, and Western blot analysis were performed to test the effects of HDAC4 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on hESCs. RNA pull-down and luciferase reporter assays were performed to validate the relationship between genes. In this study, the characteristics of hESCs were sustained in serum-free medium during a process of propagation. HDAC4 knockdown suppressed hESCs viability and promoted hESCs apoptosis. HDAC4 was targeted by miR-498-3p in hESCs. MALAT1 bound with miR-498-3p in hESCs. HDAC4 expression was positively regulated by MALAT1 and negatively regulated by miR-498-3p in hESCs. HDAC4 upregulation countervailed the effects of MALAT1 silencing on hESCs proliferation, apoptosis, and decidualization of hESCs. Overall, MALAT1 facilitated the decidualization of hESCs via binding with miR-498-3p and upregulating HDAC4, which might provide a new direction for the maintenance of a successful pregnancy.

show abstract

“…(+)-Strebloside ( 1 ) was found to induce human ovarian cancer cell apoptosis [ 11 ], for which histone deacetylases (HDACs) have been proposed as important targets [ 39 , 40 ]. Following our previous molecular docking investigation for digoxin [ 14 ], five crystal structures from different HDAC groups were selected as the receptors for docking with (+)-strebloside ( 1 ) and strophanthidin ( 10 ), including HDAC7 (PDB entry 3C10), HDAC1 (PDB entry 4BKX), HDAC8 (PDB entry 5DC8), HDAC6 (PDB entry 5EDU), and HDAC4 (PDB entry 5ZOO).…”

Section: Resultsmentioning

confidence: 99%

Interaction of (+)-Strebloside and Its Derivatives with Na+/K+-ATPase and Other Targets

Ren

Chen

et al. 2021

Molecules

View full text Add to dashboard Cite

Docking profiles for (+)-strebloside, a cytotoxic cardiac glycoside identified from Streblus asper, and some of its derivatives and Na+/K+-ATPase have been investigated. In addition, binding between (+)-strebloside and its aglycone, strophanthidin, and several of their other molecular targets, including FIH-1, HDAC, KEAP1 and MDM2 (negative regulators of Nrf2 and p53, respectively), NF-κB, and PI3K and Akt1, have been inspected and compared with those for digoxin and its aglycone, digoxigenin. The results showed that (+)-strebloside, digoxin, and their aglycones bind to KEAP1 and MDM2, while (+)-strebloside, strophanthidin, and digoxigenin dock to the active pocket of PI3K, and (+)-strebloside and digoxin interact with FIH-1. Thus, these cardiac glycosides could directly target HIF-1, Nrf2, and p53 protein–protein interactions, Na+/K+-ATPase, and PI3K to mediate their antitumor activity. Overall, (+)-strebloside seems more promising than digoxin for the development of potential anticancer agents.

show abstract

HDAC4 Knockdown Induces Preeclampsia Cell Autophagy and Apoptosis by miR-29b

Cited by 20 publications

References 23 publications

Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase and Other Targets for the Inhibition of Cancer Cell Proliferation

Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase and Other Targets for the Inhibition of Cancer Cell Proliferation

LncRNA MALAT1 promotes decidualization of endometrial stromal cells via sponging miR‐498‐3p and targeting histone deacetylase 4

Interaction of (+)-Strebloside and Its Derivatives with Na+/K+-ATPase and Other Targets

Contact Info

Product

Resources

About