Combined detection of the expression of Nm23-H1 and p53 is correlated with survival rates of patients with stage II and III colorectal cancer

Wu, Yinying; Li, Yi; Zhao, Xianda; Dong, Diansheng; Tang, Chunhui; Li, Enxiao; Geng, Qing

doi:10.3892/ol.2016.5425

Cited by 9 publications

(10 citation statements)

References 32 publications

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“…NME1 plays a significant role in regulation of p53 function 23 , 24 . NME1 stabilizes p53 by interacting with p53 and suppressing the interaction of p53 with MDM2 25 .…”

Section: Resultsmentioning

confidence: 99%

Foot-and-mouth disease virus induces lysosomal degradation of NME1 to impair p53-regulated interferon-inducible antiviral genes expression

et al. 2018

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Nucleoside diphosphate kinase 1 (NME1) is well-known as a tumor suppressor that regulates p53 function to prevent cancer metastasis and progression. However, the role of NME1 in virus-infected cells remains unknown. Here, we showed that NME1 suppresses viral replication in foot-and-mouth disease virus (FMDV)-infected cells. NME1-enhanced p53-mediated transcriptional activity and induction of interferon-inducible antiviral genes expression. FMDV infection decreased NME1 protein expression. The 2B and VP4 proteins were identified as the viral factors that induced reduction of NME1. FMDV 2B protein has a suppressive effect on host protein expression. We measured, for the first time, VP4-induced lysosomal degradation of host protein; VP4-induced degradation of NME1 through the macroautophagy pathway, and impaired p53-mediated signaling. p53 plays significant roles in antiviral innate immunity by inducing several interferon-inducible antiviral genes expression, such as, ISG20, IRF9, RIG-I, and ISG15. VP4 promoted interaction of p53 with murine double minute 2 (MDM2) through downregulation of NME1 resulting in destabilization of p53. Therefore, 5-flurouracil-induced upregulation of ISG20, IRF9, RIG-I, and ISG15 were suppressed by VP4. VP4-induced reduction of NME1 was not related to the well-characterized blocking effect of FMDV on cellular translation, and no direct interaction was detected between NME1 and VP4. The 15–30 and 75–85 regions of VP4 were determined to be crucial for VP4-induced reduction of NME1. Deletion of these VP4 regions also inhibited the suppressive effect of VP4 on NME1-enhanced p53 signaling. In conclusion, these data suggest an antiviral role of NME1 by regulation of p53-mediated antiviral innate immunity in virus-infected cells, and reveal an antagonistic mechanism of FMDV that is mediated by VP4 to block host innate immune antiviral response.

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“…NME1 plays a significant role in regulation of p53 function 23 , 24 . NME1 stabilizes p53 by interacting with p53 and suppressing the interaction of p53 with MDM2 25 .…”

Section: Resultsmentioning

confidence: 99%

Foot-and-mouth disease virus induces lysosomal degradation of NME1 to impair p53-regulated interferon-inducible antiviral genes expression

et al. 2018

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“…O CCR é um tumor com elevadas taxas de incidência e mortalidade, [8][9] tanto no ocidente quanto no oriente, crescendo em incidência a 4,2% por ano na China. 9 O adenoma colorretal é considerado um precursor de seu desenvolvimento, 8,10 que junto a processos genéticos complexos, leva a sua origem.…”

Section: Resultsunclassified

“…O TP53, presente no cromossomo 17p, codifica a proteína p53, que é responsável pela regulação do ciclo celular. [5][6][7][8][9][10][11] A mutação do TP53, o evento mais comum nos carcinomas humanos, 4,5,11 leva ao acúmulo de p53 mutante, que tem meia vida maior que a p53 selvagem 10,[12][13] , possibilitando sua coloração e visualização no núcleo celular através da IHQ. [6][7][8][9][10][11] Sob a IHQ, o núcleo da célula apresenta grânulos marrons quando positiva para p53.…”

Section: Resultsunclassified

Avaliação Da Expressão Imunoistoquimica Da Proteína P53 No Adenocarcinoma Colorretal - Revisão Bibliográfica

Guedes¹,

Bueno²,

Oliveira³

et al. 2019

Rev Pat Tocantins

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RESUMO Introdução: O carcinoma colorretal (CCR) é um tumor que se destaca por suas taxas de incidência e mortalidade no mundo. A maioria dos CRRs se desenvolve a partir de adenomas preexistentes devido a mutações genéticas acumuladas. As mutações no gene TP53 são as mais comuns encontradas nas neoplasias malignas humanas. Sua mutação pode levar ao acúmulo da proteína p53 nuclear, que pode ser vista por métodos de imuno-histoquímica (IHQ). Atualmente, o estadiamento anatomopatológico é principal método utilizado para determinar o prognóstico de pacientes com CCR. Metodologia: Foi realizado um levantamento bibliográfico na base eletrônica PubMed utilizando os descritores: “colorectal cancer” and “p53 protein” and “immunohistochemistry”. Resultados: O CCR é um tumor com altas taxas de incidência e mortalidade no ocidente e oriente. A mutação no gene TP53 parece ser um precursor do CCR e leva ao acúmulo da p53 mutada, que é visível aos métodos de IHQ. A maioria das amostras de CCR apresentaram-se positivas para p53, o que determina um comportamento mais agressivo do tumor e também serve como um fator de prognóstico ruim. Sua superexpressão indica maior chance de metástases e redução da sobrevida. Uma vez que a mutação do TP53 é um evento precoce, a detecção precoce do CCR pode ser feita através da visualização de p53 acumulada sob IHQ. Alterações no gene TP53 são fatores de prognóstico ruim em vários tipos de câncer, incluindo o CCR. Outros marcadores e fenótipos se correlacionam com a p53 no desenvolvimento do CCR, como a vitamina D, o estrogênio e a progesterona. Por fim, em nosso estudo não foi detectado relação entre a expressão da p53, idade, gênero, invasão tumoral, e taxa de regressão. Conclusão: Pode-se inferir que o CCR é um câncer com taxas de incidência, prevalência e mortalidade significantes, e que a IHQ da p53 tem papel importante na detecção precoce e decisão do tratamento. Palavras-chave: Carcinoma colorretal; gene TP53; proteína p53; imuno-histoquímica. ABSTRACT Introduction: Colorectal cancer (CRC) is well known for its incidence and mortality rate. Most of CRCs develops from colonic adenoma, that accumulates genetic mutations. TP53 gene’s mutations are the most common mutations found in human cancers. It’s mutation leads to nuclear p53 accumulation, which can be seen by immunohistochemistry (IHC) methods. Method: A research was done in PubMed using the following words: “colorectal cancer” and “p53 protein” and “immunohistochemistry”. Resulted: The CRC is a tumor with high incidence and mortality rates in the west and in the east. A mutation in TP53 gene seems to be a precursor of the CRC and leads to the accumulation of mutated p53, seen by the IHC methods. Most of CRC samples presents positive p53, and its positivity determinate a more aggressive behavior of the tumor, leading to a poor prognosis. Its overexpression indicates bigger chances of metastasis and survival rate loss. Being an early event, TP53 mutation and the following p53 nuclear accumulation makes the detection of CRC easier by IHC methods. TP53 gene alterations are also poor prognosis factors in various types of cancer, including the CRC. Other marks and phenotypes correlate with p53 in the evolution of CRC, like the vitamin D, estrogen and progesterone. Lastly, it wasn’t detected the relation between age, gender, tumor invasion, neither regression rate. Conclusion: It can be inferred that the CRC is a cancer with significant incidence, prevalence and mortality rates, and that the IHC methods have an important role in the early detection and decision making. Keywords: Colorectal carcinoma; TP53 gene; p53 protein; immunohistochemistry.

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“…The function of nm23 in human cancer is currently unconfirmed (22,(28)(29)(30)(31), and certain reports have indicated there is a link between high expression of the nm-23 gene and its protein product with low metastatic potential of cancer (28). Nm-23 is known to be associated with early onset of familial breast and ovarian cancer (28).…”

Section: Discussionmentioning

confidence: 99%

“…Although the mechanism by which nm-23 regulates metastasis is not fully understood, experimental data have shown that nm23 serves an important role in the regulation of metastasis in a number of human cancer types (29). It was also reported that nm-23 expression was a significant factor for predicting a favorable prognosis, suggesting the anti-metastatic potential of nm-23 in NSCLC (30,31). The expression of nm23 in normal lung tissue was much higher than in cancer tissues, and was associated with staging and lymphatic metastasis, and this may suggest that the absence of nm23 expression may serve an important role in the incidence of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Inhibition effects of Yuxiao San combined with cisplatin on transplanted tumor growths via upregulation of nm‑23 and downregulation of K‑ras in Lewis lung cancer mice

et al. 2018

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Traditional Chinese medicine applied to cancer therapy has a long history. This study aimed to investigate the effect and underlying mechanism of the traditional Chinese medicine, Yuxiao San, in combination with cisplatin, on Lewis lung cancer mice. Lewis lung cancer mouse models were were established in mice, and were randomly divided into model (normal saline + egg white), cisplatin (cisplatin injection + egg white), traditional Chinese medicine (Yuxiao San + egg white) and combined medication (Yuxiao San + cisplatin injection + egg white) groups. The weight and tumor size of mice was measured every 3 days, and the number of lung surface metastasis nodules were calculated after 14 days. Nucleoside diphosphate kinase (nm-23) and K-ras expression levels in tumor tissues were determined by immunohistochemical methods and reverse transcriptionquantitative polymerase chain reaction. The results suggested that compared with the model group, cisplatin, traditional Chinese medicine and combined medication groups significantly inhibited growth of transplanted tumors, reduced the number of lung metastasis nodules, increased the inhibition rate of lung metastasis (P<0.05 or P<0.01), significantly increased tumor suppressor gene nm-23 expression and significantly downregulated oncogene K-ras expression. Among all groups, the effect of the combined medication group for inhibiting tumor growth was most favorable (P<0.01). Compared with the cisplatin group, nm-23 expression in the traditional Chinese medicine group and the combined medication group was significantly increased, and K-ras expression in the traditional Chinese medicine and combined medication groups was significantly reduced (P<0.01). To conclude, Yuxiao San and cisplatin injection effectively inhibited growth of the transplanted tumor. The underlying mechanism may be associate with nm-23 upregulation and K-ras downregulation. Therefore, the Yuxiao San and cisplatin injection may become a potential therapeutic strategy for tumor treatment.

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Combined detection of the expression of Nm23-H1 and p53 is correlated with survival rates of patients with stage II and III colorectal cancer

Cited by 9 publications

References 32 publications

Foot-and-mouth disease virus induces lysosomal degradation of NME1 to impair p53-regulated interferon-inducible antiviral genes expression

Foot-and-mouth disease virus induces lysosomal degradation of NME1 to impair p53-regulated interferon-inducible antiviral genes expression

Avaliação Da Expressão Imunoistoquimica Da Proteína P53 No Adenocarcinoma Colorretal - Revisão Bibliográfica

Inhibition effects of Yuxiao San combined with cisplatin on transplanted tumor growths via upregulation of nm‑23 and downregulation of K‑ras in Lewis lung cancer mice

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