miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

Fang,Ziling; Zhong,Min; Wang,Yi; Yuan,Xiang; Guo,Hui; Yao,Yangyang; Feng,Miao; Chen,Jun; Xiong,Jianping; Xiang,Xiaojun

doi:10.3892/ijo.2018.4646

miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

Authors:
- Ziling Fang
- Min Zhong
- Yi Wang
- Xiang Yuan
- Hui Guo
- Yangyang Yao
- Miao Feng
- Jun Chen
- Jianping Xiong
- Xiaojun Xiang
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Affiliations: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: November 26, 2018 https://doi.org/10.3892/ijo.2018.4646
Pages: 733-743

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Abstract

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.

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