Nischarin downregulation attenuates cell injury induced by oxidative stress via Wnt signaling

Guo, Zhiyong; Huang, Mina; Yuan, Yajiang; Guo, Yuanqiang; Song, Changwei; Wang, Hongyu; Dang, Xiaoqian

doi:10.1097/wnr.0000000000001536

Cited by 7 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pathways that were repeatedly associated with high NISCH expression in cancer types in which it had negative prognostic value were Wnt, Hedgehog and Notch signaling. It has been reported that NISCH may regulate some aspects of Wnt signaling [ 87 ] but the association of NISCH with Notch and Hedgehog signaling is a novel finding. Common characteristic for these three pathways is that they are cell-fate determining and their crosstalk is important in the maintenance of the cancer stem cell phenotype [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the nischarin expression across human tumor types reveals its context-dependent role and a potential as a target for drug repurposing in oncology

Ostojić,

Đurić,

Živić

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Nischarin was reported to be a tumor suppressor that plays a critical role in breast cancer initiation and progression, and a positive prognostic marker in breast, ovarian and lung cancers. Our group has found that nischarin had positive prognostic value in female melanoma patients, but negative in males. This opened up a question whether nischarin has tumor type-specific and sex-dependent roles in cancer progression. In this study, we systematically examined in the public databases the prognostic value of nischarin in solid tumors, regulation of its expression and associated signaling pathways. We also tested the effects of a nischarin agonist rilmenidine on cancer cell viability in vitro. Nischarin expression was decreased in tumors compared to the respective healthy tissues, most commonly due to the deletions of the nischarin gene and promoter methylation. Unlike in healthy tissues where it was located in the cytoplasm and at the membrane, in tumor tissues nischarin could also be observed in the nuclei, implying that nuclear translocation may also account for its cancer-specific role. Surprisingly, in several cancer types high nischarin expression was a negative prognostic marker. Gene set enrichment analysis showed that in tumors in which high nischarin expression was a negative prognostic marker, signaling pathways that regulate stemness were enriched. In concordance with the findings that nischarin expression was negatively associated with pathways that control cancer growth and progression, nischarin agonist rilmenidine decreased the viability of cancer cells in vitro. Taken together, our study lays a ground for functional studies of nischarin in a context-dependent manner and, given that nischarin has several clinically approved agonists, provides rationale for their repurposing, at least in tumors in which nischarin is predicted to be a positive prognostic marker.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of the nischarin expression across human tumor types reveals its context-dependent role and a potential as a target for drug repurposing in oncology

Ostojić,

Đurić,

Živić

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Exogenous H 2 O 2 easily enter cells through the cell membrane, resulting in the production of large amounts of ROS ( 21 ). Thus, H 2 O 2 is commonly used to simulate cellular peroxidative damage in vitro ( 22 ). There have been a number of studies on PC12 cell apoptosis induced by H 2 O 2 , and the conclusions were consistent ( 23 , 24 ).…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone protects PC12 cells against oxidative stress injury: An in vitro study of its antiapoptotic effects via the PPARγ pathway

Li,

Long,

et al. 2023

Exp Ther Med

View full text Add to dashboard Cite

To the best of our knowledge, the role of peroxisome proliferator-activated receptor γ (PPARγ) in oxidative stress-induced PC12 cell damage is unknown. Using a PC12 cell model with H 2 O 2 treatment, the present study investigated the expression levels of apoptosis-related genes and neuronal apoptosis after oxidative stress injury. The present study further investigated the protective effect and mechanism of pioglitazone, a PPARγ agonist. PC12 cells treated with H 2 O 2 were used as a model of oxidative stress injury. An MTT assay and flow cytometry were used to detect the effect of H 2 O 2 on PC12 cell viability and the protective effect of pioglitazone. A TUNEL assay was used to detect neuronal apoptosis. The expression levels of PPARγ, Bax, Bcl-2 and caspase-3 were examined by reverse transcription-quantitative PCR and western blotting. H 2 O 2 reduced PC12 cell viability in a dose- and time-dependent manner. H 2 O 2 significantly upregulated the protein expression levels of Bax and the cleaved caspase-3/caspase-3 ratio (P<0.01), decreased the protein expression levels of Bcl-2 (P<0.01), and increased the apoptosis rate of PC12 cells. Pioglitazone significantly reduced the protein expression levels of Bax and the cleaved caspase-3/caspase-3 ratio (P<0.01), increased the expression levels of Bcl-2 (P<0.01), decreased the Bax/Bcl-2 expression ratio (P<0.01) and increased the viability of H 2 O 2 -damaged PC12 cells in a dose-dependent manner. Treatment with the PPARγ antagonist GW9662 or PPARγ small interfering RNA counteracted the protective effect of pioglitazone on PC12 cells to different extents (P<0.01). Therefore, the present study reported the role of PPARγ in protecting PC12 cells against oxidative stress injury, which may lead to novel therapeutic approaches for neurodegenerative diseases.

show abstract

“…The pathways that were repeatedly associated with high NISCH expression in cancer types in which it had negative prognostic value were Wnt, Hedgehog and Notch signaling. It has been reported that NISCH may regulate some aspects of Wnt signaling (59) but the association of NISCH with Notch and Hedgehog signaling is a novel nding. Common characteristic for these three pathways is that they are cell-fate determining and their crosstalk is important in the maintenance of the cancer stem cell phenotype (43).…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis reveals that nischarin may not be the universal tumor suppressor

Ostojić

Đurić

Živić

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Scaffolding protein nischarin (NISCH) was reported to be a tumor suppressor that plays a critical role in breast cancer initiation and progression through regulation of the cytoskeleton dynamics. NISCH expression was reported to be a positive prognostic marker in breast, ovarian and lung cancers. Our group has found that in melanoma, NISCH had positive prognostic value in female patients, but negative in males. These findings opened up a question whether NISCH has tumor type-specific and sex-dependent roles in cancer progression. Results: In this study, we systematically examined in the public databases the prognostic value of NISCH in solid tumors, regulation of its expression and associated signaling pathways with the special emphasis on the possible differences between male and female cancer patients. We found that NISCH expression was decreased in tumor compared to the respective healthy tissues, and that this was most commonly due to the deletions of the NISCH gene and promoter methylation. We also report that, unlike in healthy tissues where it was located in the cytoplasm and at the membrane, NISCH could be observed in the nuclei in tumor tissues. Surprisingly, we found that in many cancer types – colon, liver, skin, ovarian, prostate, and kidney – high NISCH expression was a negative prognostic marker. Gene set enrichment analysis showed that, while there were common pathways associated with NISCH expression in all the examined cancer types, in tumors in which high NISCHexpression was a negative prognostic marker Wnt-Notch-Hedgehog signaling gene networks were enriched. Conclusions: Our study questions the current tumor suppressor status of nischarin and lays a ground for functional studies in a context-dependent manner in cancer.

show abstract

Nischarin downregulation attenuates cell injury induced by oxidative stress via Wnt signaling

Cited by 7 publications

References 40 publications

Analysis of the nischarin expression across human tumor types reveals its context-dependent role and a potential as a target for drug repurposing in oncology

Analysis of the nischarin expression across human tumor types reveals its context-dependent role and a potential as a target for drug repurposing in oncology

Pioglitazone protects PC12 cells against oxidative stress injury: An in vitro study of its antiapoptotic effects via the PPARγ pathway

Pan-cancer analysis reveals that nischarin may not be the universal tumor suppressor

Contact Info

Product

Resources

About