Regulatory Mechanism Of Kruppel-like Factor 12 In Cell Cycle And Migration Of Endometrial Cancer

[Objects]Endometrial Cancer(EC)is one of the most common gynecological malignancies in the world.The Local recurrence and distant metastasis have become important factors affecting the survival of patients.Therefore,it is essential to do some research on the development of endometrial cancer and mechanisms of invasion and metastasis.KLF12 is one of the members of the KLF family and acts as a transcription factor for eukaryotes.It is involved in various biological processes such as kidney development,lipid metabolism,decidualization of endometrial stromal cells,tumor cell proliferation,invasion and anoikis.In this study,we investigated the relationship between the expression of KLF12 and the development of endometrial carcinoma from the clinical samples,cell functions in vitro and related molecular mechanisms.The regulation of KLF12 on the cell cycle and the migration of endometrial cancer cells and related molecular mechanisms were clarified.We are aim to provide a theoretical basis for assessing whether KLF12/Notch/EMT-related molecules can be served as a new target for clinical diagnosis and treatment.[Methods]1.The expression of KLF12 mRNA and protein in endometrial carcinoma and normal endometrium were detected by qRT-PCR and immunohistochemistry.Semi-quantitative immunohistochemistry detected the correlation between the expression of KLF12 and Pathological features/classical endometrial cancer immunohistochemical molecular;2.Cell cycle distribution of two endometrial carcinoma cell lines(well differentiated endometrial carcinoma cell line Ishikawa and moderately differentiated endometrial carcinoma cell line Hec-lb)after transfection of si-KLF12 by flow cytometry;qRT-PCR and Western Blot were used to detect the expression of cell cycle related genes.3.Changes in migration ability of two endometrial cancer cell lines(well-differentiated endometrial carcinoma cell line Ishikawa and moderately differentiated endometrial carcinoma cell line Hec-lb)were examined by means of wound healing and Transwell assays.The effect of KLF12 on Notch/EMT pathway-related molecules was investigated by qRT-PCR and Western Blot.[Results]1.The expression of KLF12 in endometrial cancer was significantly increased in the mRNA and protein level;its expression is related to clinical and pathological characteristics of patients;2.Si-KLF12 can promote the G2/M phase arrest of endometrial carcinoma cells;KLF12 is involved in the regulation of CyclinBl/CDK1 expression in G2/M phase;3.KLF12 can significantly promote the migration of endometrial carcinoma cells;KLF12 is involved in the regulation of Notch/EMT pathway-related molecules.[Conclusion]This study confirmed that transcription factor KLF12 expression in endometrial cancer was increased;ER expression has great difference in varying degrees of the expression of KLF12;KLF12 promotes the process of cell mitosis through the induction of cell cycle G2/M phase transition;KLF12 promotes cell migration and is involved in the regulation of Notch/EMT pathways related molecules.