ARL6IP5 reduces cisplatin-resistance by suppressing DNA repair and promoting apoptosis pathways in ovarian carcinoma

Kim, Ji-Ye; Bahar, Entaz; Lee, Jung‐Yun; Chang, Sunhee; Kim, Se Hoon; Park, Eun Young; Im, Sung Il; Yoon, Hyonok; Kim, Hyun-Soo

doi:10.1038/s41419-022-04568-4

Cited by 8 publications

(5 citation statements)

References 46 publications

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“…We found that cisplatin induced morphological changes and reduced SKOV-3 cell viability in a dose-dependent manner, and its IC50 was approximately 20 µM ( Figure S1, Supplementary Materials ). Based on this information and previous studies reporting that cisplatin at 20 µM efficiently induces DNA damage and apoptotic death in SKOV-3 cell lines [ 33 , 34 , 35 ], we thus utilized cisplatin at 20 µM in our study. We demonstrated that cisplatin alone could significantly decrease the cell viability to about 90% and 50% after 24 h and 48 h, respectively ( Figure 1 A,B).…”

Section: Resultsmentioning

confidence: 99%

Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT

et al. 2023

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In the current study, we identified a mechanism of resveratrol (RES) underlying its anti-cancer properties against human ovarian adenocarcinoma SKOV-3 cells. We investigated its anti-proliferative and apoptosis-inducing effects in combination with cisplatin, using cell viability assay, flow cytometry, immunofluorescence study and Western blot analysis. We discovered that RES suppressed cancer cell proliferation and stimulated apoptosis, especially when combined with cisplatin. This compound also inhibited SKOV-3 cell survival, which may partly be due to its potential to inhibit protein kinase B (AKT) phosphorylation and induce the S-phase cell cycle arrest. RES in combination with cisplatin strongly induced cancer cell apoptosis through activating the caspase-dependent cascade, which was associated with its ability to stimulate nuclear phosphorylation of p38 mitogen-activated protein kinase (MAPK), well recognized to be involved in transducing environmental stress signals. RES-induced p38 phosphorylation was very specific, and the activation status of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) was not mainly affected. Taken together, our study provides accumulated evidence that RES represses proliferation and promotes apoptosis in SKOV-3 ovarian cancer cells through activating the p38 MAPK pathway. It is interesting that this active compound may be used as an effective agent to sensitize ovarian cancer to apoptosis induced by standard chemotherapies.

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Section: Resultsmentioning

confidence: 99%

Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT

et al. 2023

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“…In neurodegenerative disease, Siddique et al demonstrated that ARL6IP5 can reduce the burden of α-synuclein aggregates and improve cell survival in a cellular model of Parkinson’s disease by inducing autophagy through the prevention of ubiquitination and degradation of autophagy-related 12 protein [ 24 ]. Nevertheless, ARL6IP5 can also suppress DNA repair and promote apoptosis pathways in ovarian carcinoma cells [ 25 ]. ARL6IP5 has been reported to be expressed in the kidney and is a potential causal candidate contributing to pleiotropic pathways between CKD and hyperuricemia [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation in peripheral blood is associated with renal aging and renal function decline: a national community study

Yang,

Lai,

Chou

et al. 2024

Clin Epigenet

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Background Older patients are at risk for acute kidney injury and chronic kidney disease. Age-related increases in DNA methylation at CpG islands have been linked to aging-related diseases like cancer and cardiovascular disease, but the exact causal relationship between methylation in renal aging and other kidney diseases remains unclear. This study aimed to elucidate the methylation status of peripheral blood mononuclear cells (PBMCs) in the Asian population. Using human whole blood DNA methylation analysis from the Taiwan Biobank, we included participants with both whole blood genome-wide methylation data and follow-up data on serum creatinine. We investigated hyper- and hypomethylated genes in comparison of participants with higher and lower estimated glomerular filtration (eGFR) decline rate in overall cohort as well as in comparison of old and young participants in subgroup of participants with higher eGFR decline rate. Common genes and signaling pathways in both comparative analyses were identified. Results Among 1587 participants in the analysis, 187 participants had higher eGFR decline rate. According to the comparison of methylation in participants with different eGFR declines and at different ages, respectively, we identified common hypermethylated genes, including DNMT3A and GGACT, as well as hypomethylated genes such as ARL6IP5, CYB5D1, BCL6, RPRD2, ZNF451, and MIAT in both participants with higher eGFR decline and those of older age. We observed associations between the methylation status of signaling pathways and aging as well as renal function decline. These pathways notably included autophagy, p38 mitogen-activated protein kinases, and sirtuins, which were associated with autophagy process and cytokine production. Conclusions Through methylation analysis of PBMCs, we identified genes and signaling pathways which could play crucial roles in the interplay of renal aging and renal function decline. These findings contribute to the development of novel biomarkers for identifying at-risk groups and even for therapeutic agent discovery.

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“…For instance, the ADP ribosylation factors like GTPase 6 interacting protein 5 ( ARL6IP5 ), a kind of microtubule-associated protein, can reduce the resistance to cisplatin in OC cells by suppressing DNA repair protein and promoting apoptosis. In addition, ARL6IP5 also acts as a significant prognostic factor and tumor suppressor in OC [ 69 ]. Forkhead box protein O1 ( FOXO1 ) is the downstream target of PI3K/Akt signaling pathway, which is upregulated in EOC tissues, and its overexpression predicts the poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Identifying the Role of Oxidative Stress-Related Genes as Prognostic Biomarkers and Predicting the Response of Immunotherapy and Chemotherapy in Ovarian Cancer

Liu

Yang

Yin

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Ovarian cancer (OC) is one of the most frequently seen and fatal gynecological malignancies, and oxidative stress (OS) plays a critical role in the development and chemoresistance of OC. Materials and Methods. OS-related genes (OSRGs) were obtained from the Molecular Signatures Database. Besides, gene expression profiles and clinical information from The Cancer Genome Atlas (TCGA) were selected to identify the prognostic OSRGs. Moreover, univariate Cox regression, LASSO, and multivariate Cox regression analyses were conducted sequentially to establish a prognostic signature, which was later validated in three independent Gene Expression Omnibus (GEO) datasets. Next, gene set enrichment analysis (GSEA) and tumor mutation burden (TMB) analysis were performed. Afterwards, immune checkpoint genes (ICGs) and the tumor immune dysfunction and exclusion (TIDE) algorithm, together with IMvigor210 and GSE78220 cohorts, were applied to comprehensively explore the role of OSRG signature in immunotherapy. Further, the CellMiner and Genomics of Drug Sensitivity in Cancer (GDSC) databases were also applied in investigating the significance of OSRG signature in chemotherapy. Results. Altogether, 34 prognostic OSRGs were identified, among which 14 were chosen to establish the most valuable prognostic signature. The Kaplan-Meier (KM) analysis suggested that patients with lower OS-related risk score had better prognosis. The area under the curve (AUC) values were 0.71, 0.76, and 0.85 in 3, 5, and 7 years separately, and the stability of this prognostic signature was confirmed in three GEO datasets. As revealed by GSEA and TMB analysis results, OC patients in low-risk group might have better immunotherapeutic response, which was consistent with ICG expression and TIDE analyses. Moreover, both IMvigor210 and GSE78220 cohorts demonstrated that patients with lower OS-related risk score were more likely to benefit from anti-PD-1/L1 immunotherapy. In addition, the association between prognostic signature and drug sensitivity was explored. Conclusion. According to our results in this work, OSRG signature can act as a powerful prognostic predictor for OC, which contributes to generating more individualized therapeutic strategies for OC patients.

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ARL6IP5 reduces cisplatin-resistance by suppressing DNA repair and promoting apoptosis pathways in ovarian carcinoma

Cited by 8 publications

References 46 publications

Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT

Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT

DNA methylation in peripheral blood is associated with renal aging and renal function decline: a national community study

Identifying the Role of Oxidative Stress-Related Genes as Prognostic Biomarkers and Predicting the Response of Immunotherapy and Chemotherapy in Ovarian Cancer

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