CUL4A regulates endometrial cancer cell proliferation, invasion and migration by interacting with CSN6

Wang,Xiangrong; Chen,Tianquan

doi:10.3892/mmr.2020.11661

CUL4A regulates endometrial cancer cell proliferation, invasion and migration by interacting with CSN6

Authors:
- Xiangrong Wang
- Tianquan Chen
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Affiliations: Nursing Department, Jiangsu Union Technical Institute Nantong Health Branch, Nantong, Jiangsu 226010, P.R. China, Department of Gynecology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China
Published online on: November 3, 2020 https://doi.org/10.3892/mmr.2020.11661
Article Number: 23
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometrial cancer (EC) is a common malignant gynecological tumor arising from the endometrium, with an annually increasing morbidity and mortality. The present study aimed to investigate the functions of cullin 4A (CUL4A) in EC, as well as the underlying mechanisms. CUL4A expression was assessed in several human EC cells and normal human endometrial epithelial cells (hEECs) via reverse transcription‑quantitative polymerase chain reaction and western blotting. Subsequently, short hairpin (sh)RNA‑CULA4 was transfected into cells, and cell proliferation, invasion and migration were detected using Cell Counting kit‑8, Transwell and wound healing assays, respectively. The STRING database identified that CSN6 interacted with CULA4, and immunoprecipitation was performed to verify the interaction. Subsequently, following CUL4A knockdown, pcDNA3.1‑CSN6 was transfected into cells and its effects on cell proliferation, invasion and migration were assessed. The expression levels of matrix metallopeptidase (MMP)2, MMP9 and p53 were evaluated via western blotting. The results indicated that CUL4A was highly expressed in EC cells, compared with hEECs. CULA4‑knockdown notably inhibited EC cell proliferation, invasion and migration. The expression levels of MMP2 and MMP9 were significantly decreased, while p53 expression was enhanced following CUL4A‑knockdown. The immunoprecipitation assay verified that COP9 signalosome subunit 6 (CSN6) interacted with CULA4. Furthermore, CSN6‑overexpression alleviated the inhibitory effects of CUL4A‑knockdown on EC cell proliferation, invasion and migration. Similarly, CSN6 overexpression reversed CUL4A‑knockdown‑mediated effects on the expression of MMP2, MMP9 and p53. In summary, the results demonstrated that CUL4A regulated EC cell proliferation, invasion and migration by interacting with CSN6.

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