Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Genetics Research Center, Faculty of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
BMC Cancer. 2018 Aug 29;18(1):853. doi: 10.1186/s12885-018-4765-z.
It has been shown that the expression of potassium channel tetramerization domain containing 12 (KCTD12) as a regulator of GABAB receptor signaling is reversely associated with gastrointestinal stromal tumors. In present study we examined the probable role of KCTD12 in regulation of several signaling pathways and chromatin remodelers in esophageal squamous cell carcinoma (ESCC).
KCTD12 ectopic expression was done in KYSE30 cell line. Comparative quantitative real time PCR was used to assess the expression of stem cell factors and several factors belonging to the WNT/NOTCH and chromatin remodeling in transfected cells in comparison with non-transfected cells.
We observed that the KCTD12 significantly down regulated expression of NANOG, SOX2, SALL4, KLF4, MAML1, PYGO2, BMI1, BRG1, MSI1, MEIS1, EGFR, DIDO1, ABCC4, ABCG2, and CRIPTO1 in transfected cells in comparison with non-transfected cells. Migration assay showed a significant decrease in cell movement in ectopic expressed cells in comparison with non-transfected cells (p = 0.02). Moreover, KCTD12 significantly decreased the 5FU resistance in transfected cells (p = 0.01).
KCTD12 may exert its inhibitory role in ESCC through the suppression of WNT /NOTCH, stem cell factors, and chromatin remodelers and can be introduced as an efficient therapeutic marker.
已有研究表明,钾通道四聚化结构域包含 12 (KCTD12)作为 GABAB 受体信号调节剂的表达与胃肠道间质瘤呈负相关。在本研究中,我们研究了 KCTD12 在调节食管鳞状细胞癌(ESCC)中几种信号通路和染色质重塑因子中的可能作用。
在 KYSE30 细胞系中进行 KCTD12 的异位表达。比较定量实时 PCR 用于评估转染细胞与未转染细胞中干细胞因子的表达以及 WNT/NOTCH 和染色质重塑的几种因子。
我们观察到 KCTD12 显著下调转染细胞中 NANOG、SOX2、SALL4、KLF4、MAML1、PYGO2、BMI1、BRG1、MSI1、MEIS1、EGFR、DIDO1、ABCC4、ABCG2 和 CRIPTO1 的表达。与未转染细胞相比,迁移实验显示转染细胞的细胞迁移显著减少(p=0.02)。此外,KCTD12 显著降低了转染细胞的 5FU 耐药性(p=0.01)。
KCTD12 可能通过抑制 WNT/NOTCH、干细胞因子和染色质重塑因子在 ESCC 中发挥其抑制作用,并可作为有效的治疗标志物引入。