Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Int J Oncol. 2019 Feb;54(2):733-743. doi: 10.3892/ijo.2018.4646. Epub 2018 Nov 26.
Accumulating evidence has highlighted the critical role of cullin 4B (CUL4B) in driving tumourigenesis in several malignancies, including gastric cancer (GC); however, the mechanisms underlying CUL4B upregulation remain unclear. The dysregulation of microRNAs (miRNAs or miRs) is known to be involved in tumourigenesis. In this study, we report that the expression of miR‑381 and miR‑489 is downregulated and is negatively correlated with that of CUL4B in GC tissues and cell lines. Further analysis verified that miR‑381 and miR‑489 directly targeted CUL4B. 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. Furthermore, miR‑381/miR‑489 exerted tumour suppressive functions by inactivating the Wnt/β‑catenin pathway through the targeting of CUL4B. Taken together, the findings of this study suggest that the miR‑381/miR‑489‑mediated expression of CUL4B modulates the proliferation and invasion of GC cells via the Wnt/β‑catenin pathway, which indicates that the miR‑381/miR‑489‑CUL4B axis is critical in the control of GC tumourigenesis.
越来越多的证据强调了 Cullin 4B (CUL4B) 在几种恶性肿瘤中驱动肿瘤发生的关键作用，包括胃癌 (GC)；然而，CUL4B 上调的机制尚不清楚。miRNA（miRNA 或 miR）的失调已知与肿瘤发生有关。在这项研究中，我们报告 miR-381 和 miR-489 的表达下调，并与 GC 组织和细胞系中的 CUL4B 呈负相关。进一步分析验证了 miR-381 和 miR-489 直接靶向 CUL4B。CUL4B 沉默通过抑制 Wnt/β-catenin 通路抑制细胞增殖、迁移和侵袭。miR-381/miR-489 的过表达再现了 CUL4B 沉默的效果，而 CUL4B 的恢复否定了 miR-381/miR-489 异位表达诱导的抑制作用。此外，miR-381/miR-489 通过靶向 CUL4B 来抑制 Wnt/β-catenin 通路，从而发挥肿瘤抑制功能。总之，本研究的结果表明，miR-381/miR-489 介导的 CUL4B 表达通过 Wnt/β-catenin 通路调节 GC 细胞的增殖和侵袭，表明 miR-381/miR-489-CUL4B 轴在控制 GC 肿瘤发生中至关重要。
