Collectively, KDM5D performed its role in metastasis of gastric cancer through demethylation in the promoter of CUL4A, and it suggested us a novel target in gastric cancer treatment in male.
Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays important roles in lung cancer invasion and metastasis through the regulation of the ANXA10 tumor suppressor.
Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of CUL4A in CRC proliferation and metastasis in vitro and in vivo.
Our results show that both CUL4A and CUL4B are overexpressed in the majority of lung carcinomas (<i>P</i><sub>CUL4A</sub> <0.001 and <i>P</i><sub>CUL4B</sub> <0.001) and significantly associated with tumor size (<i>P</i><sub>CUL4A</sub> <0.001 and <i>P</i><sub>CUL4B</sub> = 0.002), lymphatic invasion (<i>P</i><sub>CUL4A</sub> = 0.004 and <i>P</i><sub>CUL4B</sub> <0.001), metastasis (<i>P</i><sub>CUL4A</sub> = 0.019 and <i>P</i><sub>CUL4B</sub> = 0.006), and advanced TNM stage (<i>P</i><sub>CUL4A</sub> <0.001 and <i>P</i><sub>CUL4B</sub> <0.001), which parallels gene amplification and abnormal activation of the canonical WNT signaling.
It was demonstrated that the expression of CUL4A protein was markedly increased in OS tissues compared with the adjacent non-cancerous tissues (ANCT) (57.8% vs. 25.6%, P = 0.019), and was associated with the distant metastases in OS patients (P = 0.016).