Xin Yongfan, Ning Shili, Zhang Liang, Cui Ming
Department of Interventional Therapy, the First hospital of Shanxi Medical University, Taiyuan, China.
Department of Acute Abdominal Surgery, the Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Cell Physiol Biochem. 2018;50(2):501-511. doi: 10.1159/000494164. Epub 2018 Oct 11.
BACKGROUND/AIMS: Lymph node metastasis is the primary cause of cancer-related death among patients with gastric cancer (GC), and cell division cycle 27 (CDC27) promotes the metastasis and epithelial-mesenchymal transition in many cancers. Till now, the mechanisms underlying CDC27-induced the epithelial-mesenchymal transition (EMT) of GC are still unclear.
We analyzed the expression levels of CDC27 and EMT-related biomarkers using immunohistochemistry and Western blot in 60 cases of GC tissues, and then GC cells with CDC27 shRNAs or plasmids were subjected to in vitro and in vivo assays, including CCK-8, wound healing and transwell assays.
The CDC27 expression was obviously increased in GC tissues, and significantly correlates with EMT-related biomarkers, lymph node metastasis and poor 5-year overall survival. Additionally, in vitro and in vivo assays demonstrated that silencing of CDC27 expression effectively inhibited GC cell proliferation, invasion and metastasis. Conversely, CDC27 overexpression led to the opposite results. Finally, we demonstrated that Twist shRNA inhibited CDC27-meditated invasion and EMT of GC cells.
CDC27 facilitates gastric cancer cell proliferation, invasion and metastasis via Twist-induced EMT; thus, this study offered a new therapy method for GC patients.
背景/目的:淋巴结转移是胃癌(GC)患者癌症相关死亡的主要原因,细胞分裂周期27(CDC27)在许多癌症中促进转移和上皮-间质转化。迄今为止,CDC27诱导胃癌上皮-间质转化(EMT)的机制仍不清楚。
我们用免疫组织化学和蛋白质印迹法分析了60例胃癌组织中CDC27和EMT相关生物标志物的表达水平,然后对携带CDC27短发夹RNA(shRNAs)或质粒的胃癌细胞进行体外和体内试验,包括CCK-8、伤口愈合和Transwell试验。
CDC27在胃癌组织中的表达明显增加,且与EMT相关生物标志物、淋巴结转移及5年总生存率低显著相关。此外,体外和体内试验表明,沉默CDC27表达可有效抑制胃癌细胞的增殖、侵袭和转移。相反,CDC27过表达则导致相反的结果。最后,我们证明Twist shRNA可抑制CDC27介导的胃癌细胞侵袭和EMT。
CDC27通过Twist诱导的EMT促进胃癌细胞的增殖、侵袭和转移;因此,本研究为胃癌患者提供了一种新的治疗方法。