Contribution of KCTD12 to esophageal squamous cell carcinoma.

Contribution of KCTD12 to esophageal squamous cell carcinoma.
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KCTD12在食管鳞状细胞癌中的作用

DOI:
10.1186/s12885-018-4765-z
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发表时间:
2018-08-29
期刊:
影响因子:
3.8
通讯作者:
Moghbeli M
Moghbeli M
中科院分区:
医学2区
文献类型:
--
作者:
Abbaszadegan MR;Taghehchian N;Li L;Aarabi A;Moghbeli M

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背景研究表明,作为GABAB受体信号调节因子的钾通道四聚化结构域12(KCTD12)的表达与胃肠道间质瘤呈负相关。在本研究中,我们检查了KCTD12在食管鳞状细胞癌(ESCC)中多个信号通路和染色质重塑因子的调节中的可能作用。方法在KYSE30细胞系中进行KCTD12异位表达。采用比较定量实时PCR评估转染细胞与未转染细胞相比干细胞因子以及属于WNT/NOTCH和染色质重塑的几个因子的表达。结果我们观察到KCTD12显着下调NANOG、SOX2、SALL4、KLF4、MAML1、PYGO2、BMI1、BRG1、MSI1、MEIS1、EGFR、DIDO1、与未转染细胞相比,转染细胞中的 ABCC4、ABCG2 和 CRIPTO1。迁移测定显示,与未转染细胞相比,异位表达细胞的细胞运动显着减少(p= 0.02)。此外,KCTD12显着降低了转染细胞的5FU耐药性(p= 0.01)。结论KCTD12可能通过抑制WNT/NOTCH、干细胞因子和染色质重塑因子发挥其在ESCC中的抑制作用,并且可以作为有效的治疗标记物引入。
BackgroundIt 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).MethodsKCTD12 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.ResultsWe 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).ConclusionsKCTD12 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.
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