Evidence map›Paper›PMID 38781180›Full record

ArticlePloS one2024

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.

Marija Ostojić, Ana Đurić, Kristina Živić, Jelena Grahovac

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Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Marija OstojićDepartment of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.
Ana ĐurićDepartment of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.ORCID 0000-0002-4440-9890
Kristina ŽivićDepartment of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.ORCID 0000-0001-8687-1541
Jelena GrahovacDepartment of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.ORCID 0000-0003-1430-8682

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Drug RepositioningGene Expression Regulation, NeoplasticNeoplasmsBiomarkers, TumorCell Line, TumorCell SurvivalDNA MethylationFemaleHumansMalePrognosisPromoter Regions, GeneticSignal TransductionBiomarkers, Tumor

Identifiers

PMID38781180
PMCPMC11115306

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.