miR-103 promotes the metastasis and EMT of hepatocellular carcinoma by directly inhibiting LATS2

Han,Li-Li; Yin,Xiao-Ran; Zhang,Shu-Qun

doi:10.3892/ijo.2018.4580

miR-103 promotes the metastasis and EMT of hepatocellular carcinoma by directly inhibiting LATS2

Authors:
- Li-Li Han
- Xiao-Ran Yin
- Shu-Qun Zhang
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Affiliations: Department of Oncology, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
Published online on: October 1, 2018 https://doi.org/10.3892/ijo.2018.4580
Pages: 2433-2444
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Improving the long‑term survival of patients with hepatocellular carcinoma (HCC) remains a challenge due to metastasis and recurrence. In this study, we demonstrate that the overexpression of miR‑103 in HCC cells promotes epithelial‑mesenchymal transition (EMT), and is associated with an enhanced metastasis and poor outcomes, as shown by western blot analysis and immunohistochemistry. Mechanistically, using reporter luciferase assay we reveal that the serine/threonine‑protein kinase, large tumor suppressor kinase 2 (LATS2), a key component of the Hippo signaling pathway, is a direct target of miR‑103 in HCC cells. Transwell assay, MTT assay and western blot analysis were performed to reveal that LATS2 can counteract the functional effects of miR‑103 on HCC metastasis, growth and EMT. The analyses of clinical data indicated that a high expression of miR‑103 correlated with a high expression of vimentin, but with a low expression of LATS2 and E‑cadherin in HCC tissues. miR‑103 also reduced yes‑associated protein (YAP) phosphorylation. On the whole, the findings of this study suggest that miR‑103 promotes HCC metastasis and EMT by directly inhibiting LATS2. Thus, targeting miR‑103/LATS2 may prove to be a promising therapeutic strategy for HCC.

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