Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance.
Elevated expression of MKRN3 in squamous cell carcinoma of the head and neck and its clinical significance.
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头颈部鳞状细胞癌中MKRN3的高表达及其临床意义
DOI：
10.1186/s12935-021-02271-6
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发表时间：
2021-10-24
影响因子：
5.8
通讯作者：
Qiu Y
中科院分区：
文献类型：
--
作者：
Zhang S;Liu C;Li G;Liu Y;Wang X;Qiu Y
头颈部鳞状细胞癌（Squamous cell carcinoma of the head and neck，SCCHN）是最常见的恶性肿瘤之一，其死亡率高。本课题组前期的研究表明，Makorin Ring Finger Protein 3（MKRN 3）可能是SCCHN肿瘤发生的关键调控因子，但其在SCCHN进展中的具体作用尚未见报道。进行免疫组织化学染色或免疫印迹分析以检测MKRN 3蛋白表达。Kaplan-Meier检验用于评估MKRN 3在总生存期和无病生存期方面的预后价值。采用亚组分析和森林图分析评价不同临床病理特征的表达差异。使用基因本体论和京都基因和基因组百科全书分析进一步研究MKRN 3的调控机制。随后，使用STRING对MKRN 3进行共表达和富集分析。通过同源模建、分子对接和western blot分析，探讨MKRN 3与其潜在靶基因P5 3的关系。结果MKRN 3在SCCHN癌组织和非癌组织中异位表达，其表达水平与高T分型和临床分期密切相关。qPCR分析显示MKRN 3在SCCHN细胞系中上调。此外，Kaplan-Meier和考克斯回归分析表明，MKRN 3高表达的SCCHN患者预后较差，MKRN 3是SCCHN的潜在预后标志物。使用基因本体论和京都基因和基因组百科全书分析，我们确定MKRN 3可能参与合成和代谢以及细胞生长、死亡和运动的调节，以及与SCCHN进展相关的癌症途径。机制研究进一步揭示了MKRN 3的潜在靶点P53可能参与了MKRN 3介导的SCCHN肿瘤的发生。我们的结论是，MKRN 3代表SCCHN中有价值的预测生物标志物和潜在的治疗靶点。
BackgroundSquamous cell carcinoma of the head and neck (SCCHN) is one of the most common types of cancer that cause a substantial number of cancer-related deaths. Our previous study has revealed that makorin ring finger protein 3 (MKRN3) may act as a key regulator of the SCCHN tumorigenesis; however, its specific role in SCCHN progression has not been reported.MethodsThe Cancer Genome Atlas (TCGA) data analysis and quantitative polymerase chain reaction (qPCR) were used to quantify the MKRN3 mRNA expression levels in SCCHN; immunohistochemical staining or immunoblotting analyses were performed to detect MKRN3 protein expression. Kaplan–Meier plotter was used to assess the prognostic values of MKRN3 in terms of overall survival and disease-free survival. The expression differences based on various clinicopathological features were evaluated using subgroup analysis and forest map analysis. The regulatory mechanism of MKRN3 was further investigated using gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, STRING was used to perform a co-expression and enrichment analysis for MKRN3. Homologous modeling, molecular docking, and western blot analyses were performed to investigate the relationship between MKRN3 and its potential target gene P53.ResultsMKRN3 was ectopically expressed between cancerous and noncancerous SCCHN tissues, and its expression level was tightly associated with high T classifications as well as advanced clinical stages. qPCR analysis revealed that MKRN3 was upregulated in the SCCHN cell line. Moreover, Kaplan–Meier and Cox regression analyses indicated that SCCHN patients with high MKRN3 expression had poorer prognosis and that MKRN3 was a potential prognostic marker for SCCHN. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we determined that MKRN3 may be involved in the regulation of synthesis and metabolism and cell growth, death and motility, as well as cancer pathways associated with SCCHN progression. Mechanism investigation further revealed that P53, a potential target of MKRN3, may be involved in the SCCHN tumorigenesis mediated by MKRN3.ConclusionsWe performed a comprehensive evaluation of the clinical significance of MKRN3 and explored its underlying mechanisms. We concluded that MKRN3 represents a valuable predictive biomarker and potential therapeutic target in SCCHN.
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影响因子：
64.5
作者：
Sanchez-Vega F;Mina M;Armenia J;Chatila WK;Luna A;La KC;Dimitriadoy S;Liu DL;Kantheti HS;Saghafinia S;Chakravarty D;Daian F;Gao Q;Bailey MH;Liang WW;Foltz SM;Shmulevich I;Ding L;Heins Z;Ochoa A;Gross B;Gao J;Zhang H;Kundra R;Kandoth C;Bahceci I;Dervishi L;Dogrusoz U;Zhou W;Shen H;Laird PW;Way GP;Greene CS;Liang H;Xiao Y;Wang C;Iavarone A;Berger AH;Bivona TG;Lazar AJ;Hammer GD;Giordano T;Kwong LN;McArthur G;Huang C;Tward AD;Frederick MJ;McCormick F;Meyerson M;Cancer Genome Atlas Research Network;Van Allen EM;Cherniack AD;Ciriello G;Sander C;Schultz N
通讯作者：
Schultz N
由印记基因MKRN3突变引起的中央早熟青春期。
DOI：
10.1056/nejmoa1302160
发表时间：
2013-06-27
期刊：
The New England journal of medicine
影响因子：
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作者：
Abreu AP;Dauber A;Macedo DB;Noel SD;Brito VN;Gill JC;Cukier P;Thompson IR;Navarro VM;Gagliardi PC;Rodrigues T;Kochi C;Longui CA;Beckers D;de Zegher F;Montenegro LR;Mendonca BB;Carroll RS;Hirschhorn JN;Latronico AC;Kaiser UB
通讯作者：
Kaiser UB
影响因子：
4.1
作者：
Macedo, Delanie Bulcao;Brito, Vinicius Nahime;Latronico, Ana Claudia
通讯作者：
Latronico, Ana Claudia
影响因子：
64.8
作者：
Jiang, Le;Kon, Ning;Li, Tongyuan;Wang, Shang-Jui;Su, Tao;Hibshoosh, Hanina;Baer, Richard;Gu, Wei
通讯作者：
Gu, Wei
DOI：
10.1016/s1470-2045(12)70425-4
发表时间：
2012-11
期刊：
The Lancet. Oncology
影响因子：
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作者：
Collaborative Group on Hormonal Factors in Breast Cancer
通讯作者：
Collaborative Group on Hormonal Factors in Breast Cancer