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沉默 RIPK4 通过抑制 Wnt/β-catenin 信号通路抑制骨肉瘤中的上皮-间充质转化。

Silencing of RIPK4 inhibits epithelial‑mesenchymal transition by inactivating the Wnt/β‑catenin signaling pathway in osteosarcoma.

机构信息

Department of Pediatric Orthopedics and Pediatrics, Second Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Department of Orthopedics, Wuwei City People's Hospital, Wuwei, Gansu 733000, P.R. China.

出版信息

Mol Med Rep. 2020 Mar;21(3):1154-1162. doi: 10.3892/mmr.2020.10939. Epub 2020 Jan 14.

Abstract

Receptor interacting protein kinase 4 (RIPK4) is a serine/threonine kinase that plays an important role in the regulation of cell proliferation, invasion and metastasis in several malignancies; however, its clinical significance and biological function in osteosarcoma (OS) remains unknown. In the present study, the RIPK4 expression level was significantly upregulated in OS tissues and cell lines. High RIPK4 expression was positively associated with larger sized tumors, advanced Enneking stage and poor prognosis in patients with OS. Furthermore, the results revealed that RIPK4 knockdown in the OS cell lines MG‑63 and U2OS reduced cell migration and invasion via the inhibition of epithelial‑mesenchymal transition (EMT) process, whereby E‑cadherin expression was increased and N‑cadherin and vimentin expression decreased. Mechanistically, RIPK4 knockdown inhibited EMT by inactivating the Wnt/β‑catenin signaling pathway. These findings suggest that RIPK4 may be a novel potential therapeutic target for the treatment of metastases in patients with OS.

摘要

受体相互作用蛋白激酶 4(RIPK4)是一种丝氨酸/苏氨酸激酶,在几种恶性肿瘤中细胞增殖、侵袭和转移的调节中发挥重要作用;然而,其在骨肉瘤(OS)中的临床意义和生物学功能尚不清楚。在本研究中,RIPK4 的表达水平在 OS 组织和细胞系中明显上调。RIPK4 高表达与 OS 患者肿瘤体积较大、Enneking 分期较高和预后不良呈正相关。此外,研究结果表明,在 OS 细胞系 MG-63 和 U2OS 中敲低 RIPK4 通过抑制上皮间质转化(EMT)过程减少细胞迁移和侵袭,从而增加 E-钙黏蛋白表达,降低 N-钙黏蛋白和波形蛋白表达。机制上,RIPK4 敲低通过使 Wnt/β-连环蛋白信号通路失活来抑制 EMT。这些发现表明,RIPK4 可能是治疗 OS 患者转移的一种新的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d7/7002986/8e83a481dd5a/MMR-21-03-1154-g00.jpg

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