Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy

Sun, Xin; Shu, Yuhan; Ye, Guiqin; Wu, Chengyuan; Xu, Mengting; Gao, Ruilan; Huang, Dongsheng

doi:10.1016/j.apsb.2021.07.003

Cited by 36 publications

(27 citation statements)

References 74 publications

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“… Armenta-Castro et al (2020 ) reported that histone H3K9 and H3K14 acetylation at the promoter of LGALS9 genes is tightly associated with the protein level of Galectin-9, and the LGALS9 gene presented higher levels of histone acetylation in normal cervical cells than in cancer cells. Sun et al (2022 ) also reported that the inhibition of HDACs can activate mitophagy by mediating Parkin acetylation and leading to the inhibition of cervical cancer cell proliferation. Valproic acid/sodium valproate (VPA), a well-known antiepileptic agent, inhibits histone deacetylases, induces histone hyperacetylation, promotes DNA demethylation, and affects the histone methylation status in some cell models.…”

Section: Discussionmentioning

confidence: 96%

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients

et al. 2022

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Background: Cervical cancer is the second most lethal malignancy among women, and histone modification plays a fundamental role in most biological processes, but the prognostic value of histone modification in cervical cancer has not been evaluated.Methods: A total of 594 cervical cancer patients from TCGA-CESC, GSE44001, and GSE52903 cohorts were enrolled in the current study, along with the corresponding clinicopathological features. Patients with a follow-up time less than one month were removed. A total of 122 histone modification-associated signaling pathways were obtained from the MSigDB. The activation scores of these pathways were evaluated using the “GSVA” package, differentially expressed genes were identified by the “limma” package, and pathway enrichment was conducted using the “clusterProfiler 4.0” package. The subsequent least absolute shrinkage and selection operator (LASSO) regression analysis was performed using the “glmnet” package, and a prognostic nomogram was established using the “regplot” package. For the prediction of potential therapeutic drugs, we used the data from GDSC2016 and visualized them via “MOVICS”.Results: Nine of 23 histone modification-associated prognostic genes were identified to construct the prognostic signature by LASSO analysis, named the histone modification-associated gene (HMAG) signature. Cervical patients with HMAG-H in TCGA-CESC cohort showed a 2.68-fold change of death risk, with the 95% CI from 1.533 to 4.671 (p < 0.001), as well as the increased death risk of HMAG-H in the GSE44001 cohort (HR: 2.83, 95% CI: 1.370–5.849, p = 0.005) and GSE44001 cohort (HR: 4.59, 95% CI: 1.658–12.697, p = 0.003). We observed the preferable AUC values of the HMAG signature in TCGA-CESC cohort (1-year: 0.719, 3-year: 0.741, and 5-year: 0.731) and GSE44001 cohort (1-year: 0.850, 3-year: 0.781, and 5-year: 0.755). The C-index of the nomogram showed a prognostic value as high as 0.890, while the C-index for age was only 0.562, and that for grade was only 0.542. Patients with high HMAG scores were more suitable for the treatment of CHIR-99021, embelin, FTI-277, JNK-9L, JQ12, midostaurin, PF-562271, pyrimethamine, and thapsigargin, and patients with low HMAG scores were more suitable for the treatment of BMS-536924, CP466722, crizotinib, PHA-665752, rapamycin, and TAE684.Conclusion: We comprehensively evaluated the histone modification status in cervical cancer patients and revealed histone modification-associated prognostic genes to construct the HMAG signature, aiming to provide a new insight into prognosis prediction and precise clinical treatment.

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Section: Discussionmentioning

confidence: 96%

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients

et al. 2022

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“…en, PINK1 recruited Parkin through a series of responses. Parkin was phosphorylated, and its spatial structure changed [30]. Parkin ubiquitinated proteins on the outer membrane of mitochondria, which are recognized by p62.…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous Electrical Acupoint Stimulation Ameliorates Cognitive Function through PINK1/Parkin Mediated Mitophagy in VD Rats

Wen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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In this study, we investigated whether transcutaneous electrical acupoint stimulation (TEAS) could improve cognitive function in VD rats by regulating PINK1/Parkin-mediated mitophagy. VD rat model was prepared by modified 2-vessel occlusion (2-VO) and randomly divided into four groups: Sham group (Sham), Model group (Model), TEAS group (TEAS), and TEAS + 3-MA group (T +3 -MA). In the T +3 -MA group, autophagy inhibitor (3-MA) was injected into the lateral ventricle. After modeling, Y maze (YM), new object recognition test (NORT), Morris water maze (MWM), immunofluorescence, and Western blot were used to observe the effects of TEAS on VD rats. Behavioral experiments revealed that TEAS effectively improved the learning and memory ability of VD rats. Immunofluorescence results showed that TEAS could upregulate LC3 expression. Western blot results showed that TEAS upregulated the expression of PINK1, Parkin, and LC3-II, and downregulated the expression of LC3-I and p62 in VD rats. T +3 -MA group shows the opposite trend to TEAS group. This study demonstrates that TEAS ameliorates cognitive function through PINK1/Parkin-mediated mitophagy in VD rats.

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“…Parkin mutations exist in a variety of malignant tumors, such as colon cancer, 181 PC, 182 and cervical cancer. 183 However, Parkin is also a causative gene related to Parkinson's disease (PD). It has a neuroprotective effect, and mutations in Parkin lead to the loss of dopaminergic neurons in the substantia nigra.…”

Section: Phosphorylationmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy

Cited by 36 publications

References 74 publications

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients

Transcutaneous Electrical Acupoint Stimulation Ameliorates Cognitive Function through PINK1/Parkin Mediated Mitophagy in VD Rats

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

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