Chandran Manimegalai Swathi, Krishnamoorthy Sathiya Priya, Kalimuthu Vignesh, Thirunavukarasu Ramani Devi, Chandrabose Sureka, Balamuthu Kadalmani
Department of Animal Science, Bharathidasan University, Tiruchirappalli, Tamilnadu, 620024, India.
Ramakrishna Medical Centre LLP, Tiruchirappalli, Tamilnadu, 620003, India.
Med Oncol. 2025 Mar 20;42(4):124. doi: 10.1007/s12032-025-02676-7.
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.
子宫内膜癌是最常见的妇科恶性肿瘤。尽管治疗取得了进展，但许多患者仍会出现疾病复发或转移。本研究调查了siRNA介导的NCoR1和DLK1基因敲低对子宫内膜癌细胞系Ishikawa和AN3CA以及正常HEK 293细胞增殖的影响。使用荧光染料证明了在子宫内膜癌细胞系中预先设计的siRNAs处理前后的细胞生长和存活情况。分析了未处理的HEK 293、Ishikawa和AN3CA细胞系中BID、BAX、BCL2、半胱天冬酶3、8和9、GPR78、EGFR、VEGF、NCoR1、DLK1和ARID1A的mRNA表达，以证实Ishikawa和AN3CA细胞系的致癌特性。然后，为了证明NCoR1和DLK1基因在子宫内膜癌细胞中的成功转染，还验证了转染前后靶向基因的mRNA和蛋白质表达。结果，BID、BAX、BCL2、GPR78、EGFR和VEGF的mRNA表达显著增加。另一方面，与对照细胞系（HEK 293）相比，Ishikawa和AN3CA中的半胱天冬酶3、8和9下调。siRNA介导的转染中NCoR1和DLK1的mRNA和蛋白质表达通过干扰Notch、MAPK、SWI/SNF和NF-κB等某些途径支持子宫内膜癌细胞增殖的减少，这些途径在受体对组蛋白重塑的分级中起关键作用。基于这些发现，该研究建议探索NCoR1和DLK1的可能作用和相互作用，以及有利于子宫内膜癌进展的信号通路。
