MDM4 contributes to the increased risk of glioma susceptibility in Han Chinese population

Sun, Peng; Yan, Feng; Fang, Wenhua; Zhao, Junjie; Hu, Chen; Ma, Xudong; Song, Jinning

doi:10.1038/s41598-018-29468-6

Cited by 5 publications

(4 citation statements)

References 49 publications

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“…Nesse ínterim, foram identificados 104 genes comuns relacionados à sobrevivência de pacientes com gliomas, sendo a maioria desses genes envolvidos em vias de sinalização relacionadas com células que afetam a proliferação celular, apoptose e angiogênese (HSU et al, 2019). Além disso, foi detectado um polimorfismo de nucleotídeo único (SNP), principalmente o SNP rs4252707, que está intrínsecamente relacionado com o gene MDM4, o que demonstra um intenso desequilíbrio de ligação com o rs12031912 e rs12028476, que apesar de poucos estudos, limitados em populações europeias, podem sugerir uma interação com a patogênese do glioblastoma (SUN et al, 2018).…”

Section: Resultsunclassified

Fatores predisponentes para glioblastoma multiforme em adultos hígidos

Caetano,

De Castro,

De Moura

et al. 2024

Cuad. Ed. Desar.

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O glioblastoma multiforme (GBM) é o tumor mais agressivo entre os gliomas cerebrais, sendo uma das neoplasias malignas mais recorrentes nos Estados Unidos da América, de caráter multifatorial e evolução rápida. O objetivo deste estudo é descrever de forma sistemática por meio de levantamentos bibliográficos, quais são os fatores predisponentes para a manifestação de glioblastoma multiforme em adultos hígidos e como esses podem estar associados ao prognóstico dos pacientes. O presente trabalho trata-se de uma revisão sistemática da literatura, descritiva e qualitativa, utilizando-se da estratégia de análise “PICo”, tendo como pergunta norteadora “Quais os fatores predisponentes para glioblastoma multiforme em adultos hígidos?”, como população adultos hígidos, sendo o interesse do estudo descrever os fatores de risco associados ao glioblastoma multiforme e para o contexto, glioblastoma multiforme. Além disso, foi utilizado para embasamento teórico, o levantamento bibliográfico na base de dados PubMed utilizando-se como Descritores em Ciências da Saúde (DeCS): Glioblastoma AND Risk Factors AND Adult. Foram encontrados inicialmente 91 artigos e após a implementação de critérios de inclusão e exclusão foram encontrados 33 artigos para compor a revisão. Foi encontrado que os glioblastomas representam 1/4 dos casos de gliomas cerebrais primários, tendo como principal fator de risco o genoma dos indivíduos. Além disso, foram juntamente descritos outros fatores predisponentes, dentre eles condições de hábito e estilo de vida, como o IMC, etilismo, sedentarismo, ingestão alimentar e condições de higiene genital, além de fatores intrínsecos e individuais, como tipologia sanguínea, HAS, altura e idade e fatores mentais e psiquiátricos correlacionados, dentre outras fenômenos podem agir como fatores de predisposição ou de proteção para o GBM. Portanto, conclui-se que o GBM promove mal prognóstico nos pacientes, devido principalmente a fatores genéticos, mas não exclusivamente. Também foi apresentado como fatores de risco associados, outras condições vinculadas aos comportamentos biopsicossociais dos indivíduos suscetíveis. Todavia este estudo e temática apresenta muitas limitações, necessitando de mais pesquisas no assunto.

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Section: Resultsunclassified

Fatores predisponentes para glioblastoma multiforme em adultos hígidos

Caetano,

De Castro,

De Moura

et al. 2024

Cuad. Ed. Desar.

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show abstract

“…[22][23][24] Furthermore, MDM4 has been shown to increase the hazard of GM susceptivity in the Han Chinese population. 25 Additionally, the study by Xie et al identified let-7 to bind MDM4 and contribute to the DNA damage response in GM. 26 Thus, these reports together with our analysis implicate MDM4, and its regulators and targets to be involved in tumor formation and progression in GM.…”

Section: Discussionmentioning

confidence: 99%

<p>Elevation in the Expression of circ_0079586 Predicts Poor Prognosis and Accelerates Progression in Glioma via Interactions with the miR-183-5p/<em>MDM4</em> Signaling Pathway</p>

Chen

Liu

Wang

et al. 2020

OTT

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Purpose: Glioma (GM) usually presents with an aggressive behavior and has a poor survival outcome. The abnormal expression of circular RNAs (circRNAs) has already been detected in GM, and circ_0079586 was found to have an increased expression in GM tumors. Patients and Methods: We assessed the differences in the expression of circ_0079586 in GM tissues (N=60) and cell lines (N=5) using qRT-PCR. The clinical value of circ_0079586 was measured by Fisher's exact test and Kaplan-Meier and Cox regression analyses. Circ_0079586 siRNA and vector were transfected into LN229 and U251 cells, respectively, and the transfection was verified by qRT-PCR. Cell growth was evaluated by cell counting kit-8 (CCK-8). Cell apoptosis was measured using flow cytometric assay. Cell metastatic properties were measured by wound scratch and transwell experiments. Subcellular fractionation was used to identify the location of circ_0079586. Dual-luciferase reporter test was utilized to confirm the interaction between miR-183-5p and circ_0079586/ MDM4 3ʹ-UTR. Results: The expression of circ_0079586 was elevated in GM samples and cells and correlated with the clinical severity and unfavorable prognosis of the patients. The elevated expression of circ_0079586 led to an increase in cell growth, migration and invasion but inhibited apoptosis in U251 cells, whereas its down-regulation reversed these effects in the LN229 cells. Mechanistically, we found circ_0079586 to be primarily located in the cytoplasm of GM cells. Furthermore, circ_0079586 could act as a sponge for miR-183-5p and elevate MDM4 expression at the posttranscriptional level. Conclusion: In summary, circ_0079586 was found to be up-regulated in GM that increased the proliferation, migration and invasion in GM cells via interaction with the miR-183-5p/ MDM4 axis. We anticipate that our study would provide newer insights into the mechanism and treatment of GM.

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“…In breast cancer, the presence of SNP34091 alone does not correlate with cancer risk (Pedram et al 2016); however, in combination with the miRNA expression profile, it predicts tumor size and lymph node infiltration (Anwar et al 2017). Other SNPs in MDMX are associated with an increased risk of glioma (rs4252707) (Sun et al 2018), prostate, and gastric cancer (rs1380576) (Sun et al 2010;Wang et al 2017b) and Parkinson's disease (rs16854023) (Cha et al 2020).…”

Section: Mdm2 and Mdmx Upstream: Regulation Occurs At Every Levelmentioning

confidence: 99%

The roles and regulation of MDM2 and MDMX: it is not just about p53

et al. 2021

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Most well studied as proteins that restrain the p53 tumor suppressor protein, MDM2 and MDMX have rich lives outside of their relationship to p53. There is much to learn about how these two proteins are regulated and how they can function in cells that lack p53. Regulation of MDM2 and MDMX, which takes place at the level of transcription, post-transcription, and protein modification, can be very intricate and is context-dependent. Equally complex are the myriad roles that these two proteins play in cells that lack wild-type p53; while many of these independent outcomes are consistent with oncogenic transformation, in some settings their functions could also be tumor suppressive. Since numerous small molecules that affect MDM2 and MDMX have been developed for therapeutic outcomes, most if not all designed to prevent their restraint of p53, it will be essential to understand how these diverse molecules might affect the p53-independent activities of MDM2 and MDMX.

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MDM4 contributes to the increased risk of glioma susceptibility in Han Chinese population

Cited by 5 publications

References 49 publications

Fatores predisponentes para glioblastoma multiforme em adultos hígidos

Fatores predisponentes para glioblastoma multiforme em adultos hígidos

<p>Elevation in the Expression of circ_0079586 Predicts Poor Prognosis and Accelerates Progression in Glioma via Interactions with the miR-183-5p/<em>MDM4</em> Signaling Pathway</p>

The roles and regulation of MDM2 and MDMX: it is not just about p53

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