期刊目次

加入编委

期刊订阅

添加您的邮件地址以接收即将发行期刊数据:

Open Access Article

International Journal of Clinical Research. 2022; 6: (2) ; 163-169 ; DOI: 10.12208/j.ijcr.20220082.

Expression and clinical significance of CDC45 and CDK4 in hepatocellular carcinoma and their effects on proliferation, invasion and apoptosis of HCC cells
CDC45及CDK4在肝细胞癌中的表达、临床意义及其对HCC细胞增殖、侵袭及凋亡的影响

作者: 李贵全 *, 兰春斌, 徐竹林, 胥彬, 邓小凡

邛崃市医疗中心医院 四川邛崃

*通讯作者: 李贵全,单位:邛崃市医疗中心医院 四川邛崃;

发布时间: 2022-04-26 总浏览量: 462

摘要

目的 探讨CDC45及CDK4在肝细胞癌中的表达、临床意义及其对HCC细胞增殖、侵袭及凋亡的影响,为揭示肝细胞癌发病机制提供实验依据。方法 选取2019年6月至2021年5月院收治的肝细胞癌患者20例为研究对象。人肝细胞癌细胞 SK-N-SH购自美国ATCC公司。应用SPSS21.0统计学软件分析数据。结果 与肿瘤旁组织比较,肝细胞癌组织中CDC45的表达水平显著降低(P<0.05),CDK4的表达水平显著升高(P<0.05)。相较于miR-NC组,CDC45组SK-N-SH细胞活力显著降低,组间差异有统计学意义(P<0.05),迁移与侵袭细胞数显著减少(P<0.05),Cyclin D1、MMP-2蛋白表达水平显著降低,组间差异有统计学意义(P<0.05),P21、E-cadherin蛋白表达水平显著升高,组间差异有统计学意义(P<0.05)。Western blot检测结果显示,与miR-NC组比较,CDC45组SK-N-SH细胞中CDK4的表达水平显著降低,组间差异有统计学意义(P<0.05);与anti-miR-NC组相比,anti-CDC45组SK-N-SH细胞中CDK4的表达水平显著升高(P<0.05)。结论 CDC45在肝细胞癌组织中呈低表达,CDK4在肝细胞癌组织中呈高表达,体外细胞实验结果显示抑制CDK4的表达可抑制肝细胞癌细胞增殖、迁移及侵袭,表明沉默CDK4基因表达可能通过抑制MMP-2表达而抑制黑色素瘤细胞增殖及侵袭。

关键词: CDC45;CDK4;肝细胞癌

Abstract

Objective: To investigate the expression and clinical significance of CDC45 and CDK4 in hepatocellular carcinoma and their effects on the proliferation, invasion and apoptosis of HCC cells, and to provide experimental basis for revealing the pathogenesis of hepatocellular carcinoma.
Methods Twenty patients with hepatocellular carcinoma who were admitted to our hospital from June 2019 to May 2021 were selected as the research objects. Human hepatocellular carcinoma cells SK-N-SH were purchased from ATCC Company, USA. SPSS 21.0 statistical software was used to analyze the data.
Results Compared with the adjacent tissue, the expression level of CDC45 in hepatocellular carcinoma tissue was significantly decreased (P<0.05), and the expression level of CDK4 was significantly increased (P<0.05). Compared with the miR-NC group, the viability of SK-N-SH cells in the CDC45 group was significantly decreased, and the difference between the groups was statistically significant (P<0.05). The expression level of -2 protein was significantly decreased, and the difference between groups was statistically significant (P<0.05). The protein expression levels of P21 and E-cadherin were significantly increased, and the difference between groups was statistically significant (P<0.05). Western blot results showed that compared with the miR-NC group, the expression level of CDK4 in SK-N-SH cells in the CDC45 group was significantly decreased, and the difference between the groups was statistically significant (P<0.05). Compared with the anti-CDC45 group, the expression level of CDK4 in SK-N-SH cells in the anti-CDC45 group was significantly increased (P<0.05).
Conclusion   The expression of CDC45 is low in hepatocellular carcinoma tissue, and the expression of CDK4 is high in hepatocellular carcinoma tissue. The results of in vitro cell experiments show that inhibiting the expression of CDK4 can inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells, indicating that silencing CDK4 gene expression may It inhibits the proliferation and invasion of melanoma cells by inhibiting the expression of MMP-2.

Key words: CDC45; CDK4; Hepatocellular carcinoma

参考文献 References

[1] 范俣琳,刘瑞瑾,丁晓艳,等. 鱼藤素抑制MCF-7、H1299增殖及下调微小染色体维系蛋白3、CDC45表达[J]. 南方医科大学学报,2017,37(11):1545-1550. DOI:10.3969/j.issn.1673-4254.2017.11.20.

[2] 龙焕屏,李光. 肺腺癌预后不良的重要基因CDC20、CCNB2和CDC45[J]. 中国医科大学学报,2021,50(9): 846-850,855. DOI:10.12007/j.issn.0258-4646.2021.09.017.

[3] 彭慧湃,赵红艳,雷超,等. 马氏珠母贝细胞周期分裂基因CDC45基因特征、表达量与性状相关分析[J]. 广东海洋大学学报,2016,36(6):1-8. DOI:10.3969/j.issn.1673-9159.2016.06.001.

[4] 王毅,巩纯秀. CDC45突变引起Meier-Gorlin综合征1例报告[J]. 中国实用儿科杂志,2021,36(6):478-480. DOI:10.19538/j.ek2021060617.

[5] 常春,王静萱. CDK4/6抑制剂治疗乳腺癌的研究进展[J]. 现代肿瘤医学,2021,29(17):3120-3124.DOI:10.3969/j.issn.1672-4992.2021.17.037.

[6] 洪梦实,吕飞. CDK4/6抑制剂abemaciclib专利技术分析[J]. 广东化工,2021,48(14):124-127,123.DOI:10.3969/j.issn.1007-1865.2021.14.047.

[7] 崔松体,左坦坦,李照义. CDK4及CD133在骨肉瘤组织中的表达及临床意义[J]. 实用癌症杂志,2021, 36(5): 749-752. DOI:10.3969/j.issn.1001-5930.2021.05.014.

[8] YABUUCHI H, YAMADA Y, UCHIDA T, et al. Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins[J]. EMBO Journal,2006,25(19):4663-4674.

[9] LIU P, BARKLEY LR, DAY T, et al. The Chk1-mediated S-phase checkpoint targets initiation factor Cdc45 via a Cdc25A/Cdk2-independent mechanism.[J]. The Journal of biological chemistry,2006,281(41):30631-30644.

[10] IM, JS, KI, SH, FARINA, A, et al. Assembly of the Cdc45-Mcm2-7-GINS complex in human cells requires the Ctf4/And-1, RecQL4, and Mcm10 proteins[J]. Proceedings of the National Academy of Sciences of the United States of America,2009,106(37):15628-15632.DOI:10.1073/pnas.0908039106.

[11] YARO JEAN BAPTISTE, TIONO ALFRED B., SANOU ANTOINE, et al. Risk factors associated with house entry of malaria vectors in an area of Burkina Faso with high, persistent malaria transmission and high insecticide resistance[J]. Malaria Journal,2021,20(1).DOI:10.1186/s12936-021-03926-5.

[12] 龙焕屏,李光. 肺腺癌预后不良的重要基因CDC20、CCNB2和CDC45[J]. 中国医科大学学报,2021, 50(9): 846-850,855. DOI:10.12007/j.issn.0258-4646.2021.09.017.

[13] 范俣琳,刘瑞瑾,丁晓艳,等. 鱼藤素抑制MCF-7、H1299增殖及下调微小染色体维系蛋白3、CDC45表达[J]. 南方医科大学学报,2017,37(11):1545-1550. DOI:10.3969/j.issn.1673-4254.2017.11.20.

[14] IM, JUN-SUB, KI, SANG-HEE, FARINA, ANDREA, et al. Assembly of the Cdc45-Mcm2–7-GINS complex in human cells requires the Ctf4/And-1, RecQL4, and Mcm10 proteins[J]. Proceedings of the National Academy of Sciences of the United States of America15628-15632. DOI:10.1073/pnas.0908039106.

[15] 牟丽云,邢翔飞,陈重旭,等. 吉祥草活性成分RCE-4触发内质网应激调控人宫颈癌CaSki细胞周期阻滞[J]. 中国药理学通报,2021,37(9):1224-1231. DOI:10.3969/j.issn.1001-1978.2021.09.008.

[16] 李立,吴科锋,吕应年,等. CDK4蛋白表达在口腔癌预后中的意义[J]. 肿瘤防治研究,2009,36(12):1024-1026. DOI:10.3971/j.issn.1000-8578.2009.12.009.

[17] HAYATO YABUUCHI, YOSHIKI YAMADA, TOMONORI UCHIDA, et al. Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins[J]. The EMBO Journal,2006,25(19):4663-4674. DOI:10.1038/sj.emboj.7601347.

[18] 张兵. CDK4在骨肉瘤中的研究进展[J]. 重庆医学,2021,50(21):3746-3749,3754.DOI:10.3969/j.issn.1671-8348.2021.21.030.

引用本文

李贵全, 兰春斌, 徐竹林, 胥彬, 邓小凡, CDC45及CDK4在肝细胞癌中的表达、临床意义及其对HCC细胞增殖、侵袭及凋亡的影响[J]. 国际临床研究杂志, 2022; 6: (2) : 163-169.