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GREM2 maintains stem cell-like phenotypes in gastric cancer cells by regulating the JNK signaling pathway

机译:通过调节JNK信号通路,Grem2通过调节JNK信号通路维持胃癌细胞中的干细胞样表型

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摘要

Gastric cancer (GC) is one of the major malignancies worldwide. This study was conducted to explore the mechanism by which GREM2 maintains biological properties of GC stem cells (GCSCs), and proved that GREM2 could potentially regulate the proliferation, apoptosis, invasion, migration and tumorigenic ability of GCSCs through the regulation of the JNK signaling pathway. In silico analysis was utilized to retrieve expression microarray related to GC, and differential analysis was conducted. The cell line with the highest GREM2 expression was overexpressed with GREM2 mimic, silencing GREM2 by siRNA, or treated with activator or inhibitor of the JNK signaling pathway. Subsequently, expression of GREM2, JNK signaling pathway-, apoptosis- or migration and invasion-associated factors were determined. Proliferation, migration, invasion, apoptosis of GCSCs in vitro and tumorigenic ability and lymph node metastasis of GCSCs in vivo were determined. Based on the in silico analysis of GSE49051, GREM2 was determined to be overexpressed in GC and its expression was the highest in the MKN-45 cell line, which was selected for the subsequent experiments. Silencing of GREM2 or inhibition of the JNK signaling pathway suppressed the proliferation, migration and invasion, while promoting apoptosis of GCSCs in vitro as well as inhibiting tumorigenesis and lymph node metastasis in vivo. In conclusion, the aforementioned findings suggest that the silencing of GREM2 suppresses the activation of the JNK signaling pathway, thereby inhibiting tumor progression. Therefore, GREM2-mediated JNK signaling pathway was expected to be a new therapeutic strategy for GC.
机译:胃癌(GC)是全球主要的恶性肿瘤之一。进行该研究以探讨GREM2维持GC干细胞(GCSCs)的生物学特性的机制,并证明GREM2通过监控信号传导途径的调节可能会调节GCSC的增殖,凋亡,侵袭,迁移和致致致瘤能力。在硅分析中,利用与GC相关的表达微阵列,进行差异分析。具有最高GREM2表达的细胞系对GREM2 MIMIC,通过siRNA沉默,或用JNK信号通路的活化剂或抑制剂处理。随后,确定了GREM2,JNK信号传导途径,凋亡或迁移和侵袭相关因子的表达。体内GCSCs在体外增殖,迁移,侵袭,GCSCs的凋亡,体内GCSCs的淋巴结转移和淋巴结转移。基于GSE49051的硅分析,测定GREM2在GC中过表达,其表达在MKN-45细胞系中最高,选择用于随后的实验。 Grem2的沉默或抑制JNK信号通路抑制了增殖,迁移和侵袭,同时在体外促进GCSCs的凋亡,以及抑制体内肿瘤内酯和淋巴结转移。总之,上述研究结果表明,GREM2的沉默抑制了JNK信号通路的激活,从而抑制肿瘤进展。因此,Grem2介导的JNK信号通路预计将成为GC的新治疗策略。

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