Suppressive effects of RASAL2 on renal cell carcinoma via SOX2/ERK/p38 MAPK pathway

Wang,Sen; Hao,Xiaomin; He,Sai; Liu,Changli; Wang,Qilong

doi:10.3892/etm.2020.9280

Suppressive effects of RASAL2 on renal cell carcinoma via SOX2/ERK/p38 MAPK pathway

Authors:
- Sen Wang
- Xiaomin Hao
- Sai He
- Changli Liu
- Qilong Wang
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Affiliations: Department of Urinary Surgery, Shaanxi Friendship Hospital, Xi'an, Shaanxi 710068, P.R. China, Department of Internal Medicine, Shaanxi Province Tuberculosis Hospital, Xi'an, Shaanxi 710100, P.R. China, Department of Breast Cancer, Shaanxi Province Oncology Hospital, Xi'an, Shaanxi 710061, P.R. China, Department of General Surgery, Shaanxi Friendship Hospital, Xi'an, Shaanxi 710068, P.R. China
Published online on: October 6, 2020 https://doi.org/10.3892/etm.2020.9280
Article Number: 151
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Metastatic renal cell carcinoma (RCC) is associated with poor prognosis. Ras protein activator like 2 (RASAL2) protein has been previously demonstrated to serves as a tumor suppressor in a variety of malignancies. Therefore, the aim of the present study was to investigate the role of RASAL2 in RCC. Reverse transcription‑quantitative PCR, western blot analysis and immunohistochemistry were performed to measure mRNA and protein expression in RCC tissues, whilst immunofluorescence and western blotting were performed to evaluate protein expression in RCC cells. A Cell Counting Kit‑8 and 5‑bromo‑2'‑deoxyuridine staining were applied to determine cell viability, and Transwell assays were conducted to measure RCC cell invasion and migration. RASAL2 expression was identified to be downregulated in RCC tissues, which associate negatively with RCC pathological grade. Sox2 expression, in addition to ERK1/2 and p38 MAPK phosphorylation, were demonstrated to be increased in RCC tissues. In RCC cells, RASAL2 overexpression decreased the expression of Sox2 and the activation of ERK1/2 and p38 MAPK. Physiologically, RASAL2 overexpression decreased RCC cell viability, invasion and migration. The expression of metalloproteinase‑2/9 and tissue inhibitor of metalloproteinase 1 were also identified to be decreased and increased by RASAL2 overexpression, respectively. By contrast, RASAL2 knockdown exerted opposite effects on RCC cells compared with those observed following RASAL2 overexpression. RASAL2 expression decreased RCC cell viability, migration and invasion, which was demonstrated to be associated with the inactivation of SOX2/ERK1/2/p38 MAPK signaling. These results suggest that RASAL2 may potentially serve as a potential target for the development of novel therapeutic intervention strategies against RCC.

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