MicroRNA-335 and its target Rock1 synergistically influence tumor progression and prognosis in osteosarcoma

Wang,Yong; Wang,Ningning; Zeng,Xiandong; Sun,Jie; Wang,Guangbin; Xu,Huimian; Zhao,Wei

doi:10.3892/ol.2017.5818

MicroRNA-335 and its target Rock1 synergistically influence tumor progression and prognosis in osteosarcoma

Authors:
- Yong Wang
- Ningning Wang
- Xiandong Zeng
- Jie Sun
- Guangbin Wang
- Huimian Xu
- Wei Zhao
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Affiliations: Department of Orthopedics, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Cardiology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Surgical Oncology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Pathology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110072, P.R. China, Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: March 7, 2017 https://doi.org/10.3892/ol.2017.5818
Pages: 3057-3065
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNA (miR)‑335 and Rho-associated serine-threonine protein kinase 1 (Rock1) is ectopically expressed in multiple malignant tumors including osteosarcoma. The present study aimed to clarify whether the combined ectopically expressed miR‑335 and Rock1 was correlated with clinicopathological features and prognosis in patients with osteosarcoma. The expression of miR‑335 and Rock1 in 91 osteosarcoma tissue samples and 47 noncancerous bone tissues were determined respectively by in situ hybridization and immunohistochemistry. The association between miR‑335 and Rock1 expression with the clinicopathological features of osteosarcoma was calculated using the Pearson's χ2 test. Spearman's correlation analysis was used to study the association between the miR‑335 and Rock1 expression. Survival curves were drawn using the Kaplan‑Meier method. Univariate and multivariate analysis was performed using the Cox's proportional hazard regression model to allow the prognostic values to be assessed. Expression levels of miR‑335 were significantly reduced in osteosarcoma tissues (P<0.001), compared with that in noncancerous bone tissues, while Rock1 expression was significantly increased in osteosarcoma tissues (P<0.001). A strong correlation between miR‑335 and Rock1 expression was also shown (P<0.001). Decreased miR‑335 expression was identified to be positively associated with higher clinical stage (P=0.004) and distant metastasis (P=0.016), while elevated expression levels of Rock1 was positively associated with a larger tumor size (P=0.013), higher clinical stage (P=0.027) and distant metastasis (P=0.022). The combined high expression of Rock1 and low expression of miR‑335 was clearly associated with distant metastasis (P=0.010) and a higher clinical stage (P=0.010). Patients with elevated Rock1 or decreased miR‑335 expression exhibited a worse overall survival (OS) and disease‑free survival (DFS) compared with patients with decreased Rock1 or increased miR‑335 (P<0.001 for the two). In addition, patients with decreased miR‑335 and increased Rock1 had the worst OS and DFS (P<0.001 for the two). In multivariate survival analysis, clinical stage (P=0.002 for DFS, P=0.015 for OS), distant metastasis (P=0.024 for DFS, P=0.002 for OS), low expression of miR‑335 (P<0.001 for DFS, P=0.002 for OS) and combined depressed miR‑335 and elevated Rock1 (P=0.021 for DFS, P=0.050 for OS) expression remained as the independent prognostic factors for DFS and OS. The present findings suggest that there may be an association between the combined downregulation of miR-335 and upregulation of Rock1 with tumor progression and adverse prognosis in patients with osteosarcoma.

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