Downregulation of CKS1B restrains the proliferation, migration, invasion and angiogenesis of retinoblastoma cells through the MEK/ERK signaling pathway

Zeng,Zhou; Gao,Zhao‑Lin; Zhang,Zhi‑Pei; Jiang,Hai‑Bo; Yang,Chang‑Quan; Yang,Jie; Xia,Xiao‑Bo

doi:10.3892/ijmm.2019.4183

Downregulation of CKS1B restrains the proliferation, migration, invasion and angiogenesis of retinoblastoma cells through the MEK/ERK signaling pathway

Authors:
- Zhou Zeng
- Zhao‑Lin Gao
- Zhi‑Pei Zhang
- Hai‑Bo Jiang
- Chang‑Quan Yang
- Jie Yang
- Xiao‑Bo Xia
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Affiliations: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Ophthalmology, The First People's Hospital of Changde City, Changde, Hunan 415000, P.R. China
Published online on: May 8, 2019 https://doi.org/10.3892/ijmm.2019.4183
Pages: 103-114
Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Retinoblastoma (RB) is a common neoplasm that is exhibited in individuals globally. Increasing evidence demonstrated that cyclin‑dependent kinase regulatory subunit 1B (CKS1B) may be involved in the pathogenesis of various tumor types, including multiple myeloma and breast cancer. In the present study, the hypothesis that CKS1B downregulation would effectively inhibit the proliferation, invasion and angiogenesis of RB cells through the mitogen‑activated protein kinase kinase (MEK)/extracellular signal‑regulated kinase (ERK) signaling pathway was examined. Initial investigation of the expression profile of CKS1B in RB and adjacent retina tissues was performed using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. A total of three RB cell lines, SO‑RB50, Y79 and HXO‑RB44, were examined for selection of the cell line with the highest expression of CKS1B, and human normal retinal vascular endothelial cells (ACBRI‑181) were also evaluated. CKS1B short hairpin RNA (shRNA) sequences (shRNA CKS1B‑1, shRNA CKS1B‑2 and shRNA CKS1B‑3) and negative control shRNA sequences were constructed and transfected into cells at the third generation to evaluate the role of shCKS1B and the MEK/ERK signaling pathway in RB. Furthermore, the effect of shCKS1B on cell proliferation, migration, invasion, apoptosis and angiogenesis was investigated. CKS1B was determined to be highly expressed in RB tissue, compared with adjacent retina tissue. SO‑RB50 and HXO‑RB44 cells treated with shRNA CKS1B‑1 and shRNA CKS1B‑2 were selected for the present experiments. Activation of the MEK/ERK signaling pathway increases the expression of MEK, ERK, B‑cell lymphoma 2, proliferating cell nuclear antigen, cyclin D1, vascular endothelia growth factor and basic fibroblast growth factor, enhances cell proliferation, migration, invasion and lumen formation, and decreases apoptosis. Following silencing CKS1B, the aforementioned conditions were reversed. The key observations of the present study demonstrated that shCKS1B can inhibit the proliferation, invasion and angiogenesis of RB cells by suppressing the MEK/ERK signaling pathway. Thus, CKS1B represents a potential research target in the development of therapeutics for RB.

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