Investigating the Changes in Expression Level of FOXO1 and P27 Kip Genes in Endometrial Hyperplasia Tissue Samples Compared to Normal Tissue Sample
Subject Areas :
Journal of Animal Biology
Parvin Ghaderi
1
,
Soodabeh Fallah
2
,
Hamid Reza Khaledi
3
,
Afsaneh Tehranian
4
,
Fereshteh Rahmati
5
,
Shahrzad sheikhhasani
6
1 - Department of Biochemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran
2 - Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
3 - Department of Agricultural Engineering, Yadgar Imam Khomeini (RA) Shahrari Unit, Islamic Azad University, Tehran, Iran
4 - Department of Obstetrics and Gynecology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
5 - Department of Biochemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran
6 - Department of Obstetrics and Gynecology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Received: 2022-09-14
Accepted : 2023-01-14
Published : 2023-11-22
Keywords:
Endometrium,
hyperplasia,
FOXO1,
P27 kip,
Abstract :
Endometrial hyperplasia is the irregular proliferation of endometrial glands and an increase in the ratio of gland to stroma compared to normal proliferative endometrium. Endometrial hyperplasia is one of the precursors of endometrial cancer, which is one of the most common cancers among women. The present study was conducted with the aim of investigating changes in the expression level of FOXO1 and P27 kip genes in endometrial hyperplasia tissue samples compared to normal tissue sample. In this case-control study, samples of hyperplasia with normal marginal tissue were taken from the uterine endometrium of women who referred to the women's clinic of Arash Hospital with abnormal uterine bleeding or increased endometrial thickness. Marginal normal tissue sample and hyperplasia sample were considered as control and case, respectively. The relative expression level of FOXO1 and P27 kip genes was measured by real time PCR method after total RNA extraction and cDNA synthesis, and then the data obtained from the reaction was analyzed by RQ=2-ΔΔCT method. Data were analyzed using independent t-test. The relative expression level of FOXO1 and P27 kip genes in the hyperplasia tissue sample was not significantly different compared to the control group (P>0.05.( Although the results of some studies indicate that the expression level of FOXO1 and P27KIP genes can be changed in endometrial cancer, the results of the present study showed that, contrary to expectations, there is no significant change in relative expression level of FOXO1 and P27KIP genes in hyperplasia tissue compared to normal tissue.
References:
1.Burke W.M., Orr J., Leitao M., Salom E., Gehrig P., Olawaiye A.B., Brewer M., Boruta D., Herzog T.J., Shahin F.A., 2014. SGO Clinical Practice Endometrial Cancer Working Group. Endometrial cancer: a review and current management strategies: part II. Gynecologic Oncology, 134(2):393-402.
Fader A.N., Arriba L.N., Frasure H.E., von Gruenigen V.E.J.G. 2009. Endometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorship. Gynecologic Oncology, 114(1):121-127.
Fang Q., Sang L., Du S. 2018. Long noncoding RNA LINC00261 regulates endometrial carcinoma progression by modulating miRNA/FOXO1 expression. Cell Biochemistry and Function, 36(6):323-30.
Goto T., Takano M., Albergaria A., Briese J., Pomeranz K.M., Cloke B., Fusi L., Feroze-Zaidi F., Maywald N., Sajin M., Dina R.E. 2008. Mechanism and functional consequences of loss of FOXO1 expression in endometrioid endometrial cancer cells. Oncogene, 27(1):9-19.
Khan M.A., Massey S., Ahmad I., Akhter N., Habib M., Mustafa S., Deo S.V., Husain S.A. 2022. FOXO1 gene downregulation and promoter methylation exhibits significant correlation with clinical parameters in Indian breast cancer patients. Frontiers in Genetics, 13:842943.
Korani M., Fallah S., Tehranian A., Nourbakhsh M., Samadikuchaksaraei A., Pour M.S., Maleki J. 2013. The evaluation of the FOXO1, KLF9 and YT521 genes expression in human endometrial cancer. Clinical Lab, 59(5-6):483-489.
Kousteni S. 2012. FoxO1, the transcriptional chief of staff of energy metabolism. Bone, 50(2):437-443
Kurman R.J., Ellenson L.H., Ronnett B.M. 2011. Blaustein's pathology of the female genital tract. New York: Springer.
Lees S.J., Childs T.E., Booth F.W. 2008. Age-dependent FOXO regulation of p27Kip1 expression via a conserved binding motif in rat muscle precursor cells. American Journal of Physiology-Cell Physiology, 295(5):C1238-46.
Li X., Song C., Wang K., Li N., Sun S., Li N., Zhao Z., Li M. 2019. Prognostic significance of LAPTM4B and p27kip1 expression in triple-negative breast cancer. Cancer Biomarkers, 25(1):19-27.
11.Myatt S.S., Wang J., Monteiro L.J., Christian M., Ho K.K., Fusi .L, Dina R.E., Brosens J.J., Ghaem-Maghami S., Lam E.W. 2010. Repression of FOXO1 expression by microRNAs in endometrial cancer. Cancer Research, 70(1):367.
Matsuzaki H., Daitoku H., Hatta M., Tanaka K., Fukamizu A. 2003. Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. Proceedings of the National Academy of Sciences, 100(20):11285.
Ozdegirmenci O., Kayikcioglu F., Bozkurt U., Akgul M.A., Haberal A.J.G., 2011. Comparison of the efficacy of three progestins in the treatment of simple endometrial hyperplasia without atypia. Gynecologic and Obstetric Investigation, 72(1):10-14.
Reinbolt R.E., Hays J.F. 2013. The role of PARP inhibitors in the treatment of gynecologic malignancies. Frontiers in Oncology, 3:237.
Sanderson P.A., Critchley H.O., Williams A.R., Arends M.J., Saunders P.T. 2017. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Human Reproduction Update, 23(2):232-243.
Sanaei M., Kavoosi F. 2019. Effect of 5-aza-2'-deoxycytidine in comparison to valproic acid and trichostatin A on histone deacetylase 1, DNA methyltransferase 1, and CIP/KIP family (p21, p27, and p57) genes expression, cell growth inhibition, and apoptosis induction in colon cancer SW480 cell line. Advanced Biomedical Research. 2019:8.
Xing Y.Q., Li A., Yang Y., Li X.X., Zhang L.N., Guo H. 2018. The regulation of FOXO1 and its role in disease progression. Life Sciences, 193:124-131.
Yan Y., Liu C., Zhang J., Li W., Yin X., Dong L., Pang S., Li X. 2021. SMC4 knockdown inhibits malignant biological behaviors of endometrial cancer cells by regulation of FoxO1 activity. Archives of Biochemistry and Biophysics, 712:109026.
Yun H., Park S., Kim M.J., Yang W.K., Im D.U., Yang K.R., Hong J., Choe W., Kang I., Kim S.S., Ha J. 2014. AMP‐activated protein kinase mediates the antioxidant effects of resveratrol through regulation of the transcription factor FoxO1. The FEBS Journal, 281(19):4421-4438.
20. Zhang B., Gui L.S., Zhao X.L., Zhu L.L., Li Q.W. 2015. FOXO1 is a tumor suppressor in cervical cancer. Genetics and Molecular Research, 14(2):6605-6016.
Zhang S., Gong T.T., Liu F.H., Jiang Y.T., Sun H., Ma X.X., Zhao Y.H., Wu Q.J. 2019. Global, regional, and national burden of endometrial cancer, 1990–-2017: results from the global burden of disease study, 2017. Frontiers in Oncology, 9:1440.
Zhang W., Duan N., Song T., Li Z., Zhang C., Chen X. 2017. The emerging roles of forkhead box (FOX) proteins in osteosarcoma. Journal of Cancer, 8(9):1619.
Zou J., Hong L., Luo C., Li Z., Zhu Y., Huang T., Zhang Y., Yuan H., Hu Y., Wen T., Zhuang W. 2016. Metformin inhibits estrogen‐dependent endometrial cancer cell growth by activating the AMPK–FOXO 1 signal pathway. Cancer Science, 107(12):1806-1817.
_||_