Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, China.
Neoplasma. 2019 Jan 15;66(1):92-100. doi: 10.4149/neo_2018_180325N201. Epub 2018 Sep 4.
Gastric cancer (GC) is a leading cause of global cancer-related death. The incidence and mortality rates of gastric cancer in China are second and third ranked in all forms of malignant tumors. Krüppel-like factor11 (KLF11) is a member of the KLF family, and previous studies have shown it significantly influences epithelial ovarian, pancreatic and liver cancer proliferation, differentiation and apoptosis. However, the expression and some biological functions of KLF11 in GC are still unclear. We therefore collected and analyzed the mRNA and protein expressions of KLF11 in 59 paired gastric cancer tissues and matched healthy gastric tissue samples. We then investigated the KLF 11 biological functions and potential mechanisms in BGC823 and HGC27 gastric cancer cell lines. Analysis of KLF11 in gastric cancer specimens confirmed up-regulation compared to adjacent healthy gastric tissues, and similar results were evident in the GC cell lines. Ectopic expression of KLF11 was significantly associated with GC cell invasion and migration. KLF11 functions were most effective in Twist1 expression and knockdown, and also in KLF11 up-regulation which was accompanied by corresponding change in Twist1 expression; but these effects were inhibited when KLF11 was silenced by the small interfering RNA (siRNA). The relative Twist1 promoter region activity increased gradually with increasing KLF11 plasma, and KLF11 therefore has a critical role in regulating gastric cancer migration and invasion by increasing Twist1 expression. Finally, the results of this study should improve understanding of the KLF11 and EMT regulating network and KLF11's use as a potential therapeutic target in gastric cancer.
胃癌（GC）是全球癌症相关死亡的主要原因。中国胃癌的发病率和死亡率在所有恶性肿瘤中均排名第二和第三。Krüppel 样因子 11（KLF11）是 KLF 家族的成员，先前的研究表明它显著影响上皮性卵巢癌、胰腺癌和肝癌的增殖、分化和凋亡。然而，KLF11 在 GC 中的表达和一些生物学功能仍不清楚。因此，我们收集并分析了 59 对胃癌组织和配对的健康胃组织样本中 KLF11 的 mRNA 和蛋白表达。然后，我们研究了 BGC823 和 HGC27 胃癌细胞系中 KLF11 的生物学功能和潜在机制。KLF11 在胃癌标本中的分析证实了与相邻健康胃组织相比的上调，并且在 GC 细胞系中也有相似的结果。KLF11 的异位表达与 GC 细胞的侵袭和迁移明显相关。在 Twist1 表达和敲低时，KLF11 功能最为有效，并且在 KLF11 上调时伴随着 Twist1 表达的相应变化；但当 KLF11 被小干扰 RNA（siRNA）沉默时，这些效应受到抑制。相对 Twist1 启动子区域活性随着 KLF11 血浆的增加而逐渐增加，因此 KLF11 通过增加 Twist1 表达在调节胃癌迁移和侵袭中起关键作用。最后，本研究的结果应有助于提高对 KLF11 和 EMT 调节网络的认识，并将 KLF11 作为胃癌的潜在治疗靶点。
