CUL4B silencing inhibited cell proliferation, migration and invasion by inactivating the Wnt/β‑catenin pathway. miR‑381/miR‑489 overexpression recapitulated the effects of CUL4B silencing, while CUL4B restoration negated the suppressive effects induced by the ectopic expression of miR‑381/miR‑489.
Silencing of CUL4B also resulted in decreased Wnt and β‑catenin expression, but increased expression of GSK‑3β, caspase‑3 and cyclin E. These results indirectly demonstrate that CUL4B enhances the proliferation and invasion abilities of gastric cancer cells by upregulating the constituent factors Wnt and β‑catenin, as well as by negatively regulating the mRNA and protein expression of GSK‑3β, caspase‑3 and cyclin E. The potential mechanism of CUL4B highlighted in the present study may be helpful for the treatment of patients with gastric cancer.
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.
Taken together, these results suggest that knockdown of CUL4B inhibited the proliferation and invasion through suppressing the Wnt/β-catenin signaling pathway in NSCLC cells.
We demonstrated that CUL4B promotes cell proliferation and invasion, which are consistent with a tumorigenic phenotype, at least partially by repressing IGFBP3.
Immunohistochemical study displayed that high CUL4B expression was significantly associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion, and advanced tumor stage.