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

P Ghaderi; S Fallah; H R Khaledi; A Tehranian; F Rahmati; S Sheikhhasani

doi:10.4183/aeb.2023.1

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

Acta Endocrinol (Buchar). 2023 Jan-Mar;19(1):1-9. doi: 10.4183/aeb.2023.1. Epub 2023 Aug 14.

Authors

P Ghaderi¹, S Fallah², H R Khaledi³, A Tehranian⁴, F Rahmati¹, S Sheikhhasani⁵

Affiliations

¹ Dept. of Biochemistry, Faculty of Biological Sciences, North -Tehran Branch, Islamic Azad University, Tehran, Iran.
² Dept. of Biochemistry Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
³ Dept. of Agricultural Engineering, Faculty of Technical-Engineering and Basic Sciences, Shahre Rey Branch, Islamic Azad University, Tehran, Iran.
⁴ Dept. of Obstetrics and Gynecology, Research Development Center, Arash Women's Hospital.
⁵ Obstetrician & Gynecologist - Oncologist, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Objectives: 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, P27^Kip1, miR-27, and miR-186, and Akt1, Akt-P proteins in patients with EC and endometrial hyperplasia compared to control subjects.

Subjects and methods: 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.

Results: 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). P27^Kip1 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 P27^Kip1 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).

Conclusions: 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.

Keywords: biomarker; endometrial cancer; endometrial hyperplasia.