Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, 74655The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of China.
Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211038492. doi: 10.1177/15330338211038492.
Cancer cells have properties similar to those of stem cells, including high proliferation and self-renewal ability. is the key regulatory gene that maintains the self-renewal and pluripotency characteristics of embryonic stem cells. We previously reported that knockdown of the pluripotent stem cell factor NANOG obviously reduced the proliferation and drug-resistance capabilities of esophageal squamous cell carcinoma (ESCC). In this study, we gained insights into the potential regulatory mechanism of NANOG, particularly in ESCC. NANOG was ectopically expressed in the Eca-109 cell line via pcDNA3.1 vector transfection. The mRNA expression of different genes was detected using quantitative real-time polymerase chain reaction, and protein quantification was performed by western blotting. The enzyme-linked immunosorbent assay was used to detect the expression of interleukin 6 (IL-6). The capabilities of proliferation, migration, and invasion were investigated using cell count and Transwell assays. The tumor sphere-forming assay was used to investigate the sphere formation capacity of cancer stem cells. The expression of NANOG promoted the cell proliferation and sphere formation capacity of cancer stem cells in a dose-dependent manner. IL-6-mediated activation of signal transducer and activator of transcription 3 (STAT3) was closely related to the expression of NANOG in ESCC. Consistently, the target genes of STAT3, including , , , and , were upregulated upon the overexpression of NANOG. These results revealed that the expression of NANOG promotes cell proliferation, invasion, and stemness via IL-6/STAT3 signaling in ESCC.
癌细胞具有类似于干细胞的特性，包括高增殖和自我更新能力。 是维持胚胎干细胞自我更新和多能性特征的关键调节基因。我们之前报道过，敲低多能干细胞因子 NANOG 明显降低了食管鳞状细胞癌 (ESCC) 的增殖和耐药能力。在这项研究中，我们深入了解了 NANOG 的潜在调节机制，特别是在 ESCC 中。通过 pcDNA3.1 载体转染，在 Eca-109 细胞系中外源表达 NANOG。使用实时定量聚合酶链反应检测不同基因的 mRNA 表达，并通过 Western blot 进行蛋白质定量。酶联免疫吸附试验用于检测白细胞介素 6 (IL-6) 的表达。通过细胞计数和 Transwell 分析检测增殖、迁移和侵袭能力。肿瘤球体形成试验用于研究癌症干细胞的球体形成能力。NANOG 的表达以剂量依赖性方式促进癌症干细胞的细胞增殖和球体形成能力。IL-6 介导的信号转导和转录激活因子 3 (STAT3) 的激活与 ESCC 中 NANOG 的表达密切相关。一致地，STAT3 的靶基因，包括 、 、 、和 ，在 NANOG 的过表达时上调。这些结果表明，NANOG 通过 IL-6/STAT3 信号通路促进 ESCC 中的细胞增殖、侵袭和干性。
