An investigative study on the impact of DLK1 and NCoR1 knockdown by siRNA transfection on endometrial cancer proliferation: unveiling notch interactions.

Abstract

Endometrial cancer is the most common gynecological malignancy. Despite advances in treatment, many patients experience disease recurrence or metastasis. This study investigates the impact of siRNA-mediated gene knockdown of NCoR1 and DLK1 genes in the proliferation of endometrial cancer cell lines Ishikawa and AN3CA and normal HEK 293 cells. Cellular growth and survival before and after the treatment of predesigned siRNAs in the endometrial cancer cell lines were evidenced using fluorescent stains. The mRNA expression of BID, BAX, BCL2, Caspases 3, 8, and 9 GPR78, EGFR, VEGF, NCoR1, DLK1 and ARID1A was analyzed in the untreated HEK 293, Ishikawa, and AN3CA cell lines to substantiate the oncogenic property of Ishikawa and AN3CA cell lines. Then, to evidence the successful transfection of NCoR1 and DLK1 gene in endometrial cancer cells, the mRNA and protein expression of targeted genes before and after being transfected were also validated. As a result, the mRNA expression significantly increased in BID, BAX, BCL2, GPR78, EGFR and VEGF. On the other hand, Caspases 3, 8, and 9 were down-regulated in Ishikawa and AN3CA compared to the control cell line (HEK 293). The mRNA and protein expression of NCoR1 and DLK1 in siRNA-mediated transfection supported the reduced proliferation in endometrial cancer cells by interfering with certain pathways like Notch, MAPK, SWI/SNF, and NF-κB, which have crucial roles in the grade of receptor to the histone remodeling. With these findings, the study recommends exploring the possible role and interactions of NCoR1 and DLK1, signaling pathways that favor the progression of endometrial cancer.