|本期目录/Table of Contents|

[1]张春锋,刘 沛,韩广业.MCM4促进透明细胞肾细胞癌细胞增殖的研究[J].天津医科大学学报,2025,31(01):41-46,59.[doi:10.20135/j.issn.1006-8147.2025.01.0041]
　ZHANG Chunfeng,LIU Pei,HAN Guangye.MCM4 promotes the proliferation of clear cell renal cell carcinoma cells[J].Journal of Tianjin Medical University,2025,31(01):41-46,59.[doi:10.20135/j.issn.1006-8147.2025.01.0041]
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MCM4促进透明细胞肾细胞癌细胞增殖的研究(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
31卷
期数:
2025年01期
页码:
41-46,59
栏目:
基础医学
出版日期:
2025-01-20

文章信息/Info

Title:
MCM4 promotes the proliferation of clear cell renal cell carcinoma cells
文章编号:
1006-8147(2025)01-0041-07
作者:
张春锋; 刘 沛; 韩广业
（新乡医学院第一附属医院泌尿外科，新乡453100）
Author(s):
ZHANG Chunfeng;  LIU Pei;  HAN Guangye
（Department of Urology， The First Affiliated Hospital of Xinxiang Medical University， Xinxiang 453100， China）
关键词:
微小染色体维持缺陷蛋白4; 增殖细胞核抗原透明细胞肾细胞癌; 细胞增殖
Keywords:
MCM4;  PCNA;  clear cell renal cell carcinoma;  proliferation
分类号:
R69
DOI:
10.20135/j.issn.1006-8147.2025.01.0041
文献标志码:
A
摘要:
目的：探讨微小染色体维持缺陷蛋白4（MCM4）对透明细胞肾细胞癌（ccRCC）细胞的影响。方法：GEPIA数据库分析不同肿瘤MCM4的表达，通过免疫组化染色（IHC）检测ccRCC病理标本中MCM4的表达。将HTB-47和CRL-1932细胞均各分为实验组与对照组，利用RT-PCR、Western印迹、细胞平板克隆形成实验、CCK-8实验验证MCM4对细胞生长的影响。通过GEPIA数据库建立MCM4与增殖细胞核抗原（PCNA）共表达网络，IHC验证ccRCC中MCM4和PCNA的相关性。结果：GEPIA数据库结果显示ccRCC组织中MCM4蛋白有表达，且其高表达提示不良预后（P<0.001）。IHC显示，与正常组织相比，ccRCC肿瘤组织中MCM4表达升高。临床特征显示肿瘤大小与MCM4表达水平相关（χ2=9.199，P<0.05）。在敲低MCM4基因后HTB-47和CRL-1932细胞MCM4蛋白表达下降（T=5.432、4.784，均P<0.05），细胞增殖能力降低（T=4.798、5.278、5.112、4.628，均P<0.05）。在数据库及IHC中均观察到MCM4的表达与PCNA有一致性（R=0.64， χ2=8.414，均P<0.05）。结论：MCM4在ccRCC中高表达，且与不良的临床病理特征相关。敲低MCM4基因可抑制ccRCC细胞增殖，且其与PCNA基因表达高度一致。
Abstract:
Objective： To investigate the effects of minichromosome maintenance protein 4 （MCM4）on clear cell renal cell carcinoma （ccRCC） cells. Methods： GEPIA database was used to analyze the expression of MCM4 gene in different tumors， and immunohistochemical staining （IHC） was used to detect the expression of MCM4 in ccRCC pathological specimens. HTB-47 and CRL-1932 cells were divided into experimental and control groups， and the effect of MCM4 on cell growth were verified using RT-PCR， WB， cell plate clone formation assay， and CCK-8 assay. We established a co expression network of PCNA and MCM4 using the GEPIA database， and validated the correlation between MCM4 and proliferating cell nuclear antigen（PCNA） in ccRCC using IHC. Results： The GEPIA database showed the MCM4 protein was expressed in ccRCC tissues， and its high expression suggested poor prognosis（P<0.001）. The IHC showed that MCM4 expression in ccRCC was higher than that in normal tissues， and clinical features of patients showed a correlation between tumor size and MCM4 expression levels（χ2=9.199，P<0.05）. Knocking down the MCM4 gene resulted in a decrease in MCM4 protein expression （T=5.432， 4.784， all P<0.05） and cell proliferation ability in HTB-47 and CRL-1932 cells （T=4.798，5.278，5.112， 4.628， all P<0.05）. The high and low expression of MCM4 was consistent with PCNA expression in both the database and IHC（R=0.64， χ2=8.414， all P<0.05）. Conclusion： MCM4 is highly expressed in ccRCC and is associated with adverse clinicopathological features. Knocking down the MCM4 gene can inhibit the proliferation of ccRCC cells， and its expression is highly consistent with PCNA gene expression.

参考文献/References:

[1] SIEGEL R L， MILLER K D， WAGLE N S， et al. Cancer statistics， 2023[J]. CA Cancer J Clin， 2023， 73（1）：17-48.
[2] MO M， ZHU Q， YANG L， et al. Comprehensive analysis of ETS1 expression and its prognostic value in clear cell renal cell carcinoma[J]. Am J Transl Res， 2024， 16（4）：1062-1080.
[3] ZHU D， SHI X， TIAN Y， et al. Combining expression of RNF43 and infiltration level of CD163+ tumor associated macrophage predicts prognosis of clear cell renal cell carcinoma[J]. Cancer Med， 2023， 12（4）：3962-3971.
[4] FONTES-SOUSA M， CALVO E. First-line immune checkpoint inhibitors in advanced or metastatic renal cell carcinoma with sarcomatoid features[J]. Cancer Treat Rev， 2022， 105：102374.
[5] YU Z， CHEN G， FENG Z， et al. Establishing a prognostic model based on five starvation-related long non-coding RNAs for clear cell renal cell carcinoma[J]. Aging （Albany NY）， 2023， 15（14）：6736-6748.
[6] BAHADORAM S， DAVOODI M， HSSNZADEH S， et al. Renal cell carcinoma： an overview of the epidemiology， diagnosis， and treatment[J]. G Ital Nefrol， 2022， 39（3）：2022-vol3.
[7] KOBAYASHI G， HAYASHI T， SENTANI K， et al. MCM4 expression is associated with high-grade histology， tumor progression and poor prognosis in urothelial carcinoma[J]. Diagn Pathol， 2023， 18（1）：106.
[8] TAN Y， DING L， LI G. MCM4 acts as a biomarker for LUAD prognosis[J]. J Cell Mol Med， 2023， 27（21）：3354-3362.
[9] ROST L M， RADER S B， OLAISEN C， et al. PCNA regulates primary metabolism by scaffolding metabolic enzymes[J]. Oncogene， 2023， 42（8）：613-624.
[10] ALPHEY M S， WOLFORD C B， MACNEILL S A. Canonical binding of Chaetomium thermophilum DNA polymerase δ/ζ subunit PolD3 and flap endonuclease Fen1 to PCNA[J]. Front Mol Biosci， 2023， 10：1320648.
[11] VILLEGAS-RUIZ V， ROMO-MANCILLAS A， MEDINA-VERA I， et al. The proliferating cell nuclear antigen（PCNA） transcript var-iants as potential relapse markers in B-cell acute lmphoblastic leu-kemia[J]. Cells， 2022， 11（20）：3205.
[12] SIMONEAU A， ENGEL J L， BANDI M， et al. Ubiquitinated PCNA drives USP1 synthetic lethality in cancer[J]. Mol Cancer Ther， 2023， 22（2）：215-226.
[13] PEI L P， ZHANG Y Z， LI G Y， et al. Comprehensive analysis of the expression and prognosis for MCM4 in uterine corpus endometrial carcinoma[J]. Front Genet， 2022， 13：890591.
[14] SAUER T， FACHINETTI G， KOHL M， et al. Protein expression of AEBP1， MCM4， and FABP4 differentiate osteogenic， adipogenic， and mesenchymal stromal stem cells[J]. Int J Mol Sci， 2022， 23（5）：2568.
[15] WANG W， YAN T， GUO X， et al. KAP1 phosphorylation promotes the survival of neural stem cells after ischemia/reperfusion by maintaining the stability of PCNA[J]. Stem Cell Res Ther， 2022， 13（1）：290.

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备注/Memo

备注/Memo:
作者简介：张春锋（1984-），男，主治医师，硕士，研究方向：泌尿系统疾病的诊治；通信作者：韩广业，E-mail：guangye@126.com。
更新日期/Last Update: 2025-02-10