子宫内膜癌与增生症患者中FOXO-1、P27KIP1、MIR-27、MIR-186和AKT1/AKT-P蛋白的表达水平:对人类生殖系统的意义分析。
EXPRESSION LEVELS OF FOXO-1, P27KIP1, MIR-27, MIR-186 AND AKT1/AKT-P PROTEINS IN WOMEN WITH ENDOMETRIAL CANCER AND HYPERPLASIA: IMPLICATIONS FOR THE HUMAN REPRODUCTIVE SYSTEM.
发表日期:2023
作者:
P Ghaderi, S Fallah, H R Khaledi, A Tehranian, F Rahmati, S Sheikhhasani
来源:
GENES & DEVELOPMENT
摘要:
尽管在子宫内膜癌(EC)和子宫内膜增生方面进行了广泛的研究,但对其发展和进展的分子机制仍存在缺口。本研究旨在调查与EC和子宫内膜增生患者相比对照组,FOXO-1、P27Kip1、miR-27和miR-186以及Akt1、Akt-P蛋白的表达水平。我们从就诊于伊朗德黑兰的阿拉什和伊玛穆霍梅尼医院的患者中获取了子宫内膜肿瘤(n=30),正常(对照)(n=30)和子宫内膜增生(n=30)组织的样本。我们通过qRT-PCR评估了基因和微RNA的表达水平。蛋白质评估采用了Western blot分析。采用t检验,Mann-Whitney U检验,Pearson相关系数分析,ANCOVA和ANOVA分析数据。与对照组组织相比,EC组织中的FOXO-1显著降低(p<0.05)。EC患者miR-27表达显著增加(p<0.001),而增生患者的显著增加(p<0.01),而miR-186的表达水平仅在EC患者中显著增加(p<0.05)。EC和增生患者中P27Kip1的表达水平变化不显著。EC患者中miR-27与FOXO-1和P27Kip1的表达水平之间存在显著相关性。Western blot分析显示EC和增生患者的子宫内膜AKT1-P蛋白水平高于对照组(p<0.05)。我们的研究结果表明,FOXO-1、miR-27、miR-186和Akt1-P/Akt1蛋白有潜力作为早期诊断、预后和EC进展的组织生物标志物。©2023 Acta Endocrinologica (Buc).
Despite extensive research on endometrial cancer (EC) and endometrial hyperplasia, there is still a gap in understanding the molecular mechanisms underlying their development and progression. The aim of this study was to investigate the expression levels of FOXO-1, P27Kip1, miR-27, and miR-186, and Akt1, Akt-P proteins in patients with EC and endometrial hyperplasia compared to control subjects.Samples of the endometrial tumor (n=30), normal (control) (n=30) and endometrial hyperplastic (n=30) tissue were obtained from patients referring to Arash and Imam Khomani hospitals, Tehran, Iran. Expression levels of genes and microRNAs were evaluated by qRT- PCR. Western blot analysis was applied for protein evaluation. The data were analyzed using t-test, Mann -Whitney U, Pearson correlation coefficient analysis, ANCOVA and ANOVA.There was significant decrease in FOXO-1 in EC tissue compared to control tissue (p<0.05). Significant increase was observed in expression of miR-27 in patients with EC (p<0.001) and hyperplasia (p<0.01), whereas miR-186 expression level increased significantly only in patients with EC (p<0.05). P27Kip1 expression level did not significantly change in patients with EC and hyperplasia. There was a significant association between expression levels of miR-27 with FOXO-1 and P27Kip1 in patients with EC. Western blot analysis revealed higher endometrial AKT1-P protein levels in patients with EC and hyperplasia than control subjects (p<0.05).Our findings suggest that FOXO-1, miR-27, miR-186, and Akt1-P/Akt1 protein have the potential to serve as tissue biomarkers for early diagnosis, prognosis, and progression of EC in the human reproductive system.©2023 Acta Endocrinologica (Buc).