Gao Kaituo, Yin Jijuan, Dong Jian
Department of Orthopedics, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
Int J Mol Med. 2016 Dec;38(6):1850-1856. doi: 10.3892/ijmm.2016.2800. Epub 2016 Nov 10.
WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human osteosarcoma, and the restoration of its expression can suppress tumorigenicity in WWOX-negative OS cells. However, its regulatory mechanisms remain to be fully elucidated. In the present study, we demonstrate that WWOX is downregulated and that it regulates proliferation and epithelial-to-mesenchymal transition (EMT)-associated protein expression in osteosarcoma. As shown by our results, WWOX overexpression by transfection with WWOX overexpression plasmids suppressed the proliferation, migration and invasion of osteosarcoma MG63 cells (as shown by MTT and migration and invasion assays). The silencing of microRNA (miR)‑214‑3p by transfection with anti-miR‑14‑3p upregulated WWOX protein expression and also inhibited the proliferation, migration and invasion of osteosarcoma cells. Additionally, we found that WWOX negatively regulated miR‑214‑3p and miR‑10b expression. Our findings define a negative feedback pathway in control of WWOX and miR‑214‑3p expression, thus providing novel molecular targets for the treatment of osteosarcoma.
含WW结构域的氧化还原酶（WWOX）在人类骨肉瘤中经常失活，其表达的恢复可抑制WWOX阴性骨肉瘤细胞的致瘤性。然而，其调控机制仍有待充分阐明。在本研究中，我们证明WWOX在骨肉瘤中表达下调，并且它调节骨肉瘤中的增殖以及上皮-间质转化（EMT）相关蛋白的表达。如我们的结果所示，通过转染WWOX过表达质粒使WWOX过表达可抑制骨肉瘤MG63细胞的增殖、迁移和侵袭（如MTT以及迁移和侵袭实验所示）。通过转染抗miR-14-3p使微小RNA（miR）-214-3p沉默会上调WWOX蛋白表达，并且也抑制骨肉瘤细胞的增殖、迁移和侵袭。此外，我们发现WWOX负向调节miR-214-3p和miR-10b的表达。我们的研究结果确定了控制WWOX和miR-214-3p表达的负反馈途径，从而为骨肉瘤的治疗提供了新的分子靶点。
