2. Academic Validation
  3. SIAH1-mediated RPS3 ubiquitination contributes to chemosensitivity in epithelial ovarian cancer

SIAH1-mediated RPS3 ubiquitination contributes to chemosensitivity in epithelial ovarian cancer

  • Aging (Albany NY). 2022 Aug 8;14(15):6202-6226. doi: 10.18632/aging.204211.
Lu Chen 1 2,  Wujiang Gao 1 2,  Chunli Sha 1 2,  Meiling Yang 3,  Li Lin 1 2,  Taoqiong Li 1 2,  Hong Wei 2,  Qi Chen 2,  Jie Xing 1 2,  Mengxue Zhang 1 2,  Shijie Zhao 2,  Wenlin Xu 2,  Yuefeng Li 4,  Xiaolan Zhu 1 2 5
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
  • 2 Department of Central laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
  • 3 Obstetrics and Gynecology, The First People's Hospital of Nantong City, Nantong, Jiangsu, China.
  • 4 Department of Radiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
  • 5 International Genome Center of Jiangsu University, Zhenjiang, Jiangsu, China.
PMID: 35951361 DOI: 10.18632/aging.204211
Abstract

The E3 Ligase SIAH1 is deregulated in human cancers and correlated with poor prognosis, but its contributions to chemoresistance in epithelial ovarian Cancer (EOC) are not evident. Herein we found that SIAH1 was decreased in EOC tumour tissues and cell lines and negatively correlated with the RPS3 levels. SIAH1 overexpression suppressed tumour cell growth, colony formation, invasion, metastasis, and cisplatin resistance in vivo and in vitro. SIAH1 promoted RPS3 ubiquitination and degradation using the RING-finger domain, and these steps were required for RPS3 localization to the cytoplasm, which led to subsequent NF-κB inactivation and thereby conferred chemosensitivity. Moreover, ectopic expression of RPS3 or depletion of RPS3 ubiquitination mediated by SIAH1 via the K214R mutant significantly impaired cisplatin-induced tumour suppression in cells stably expressing SIAH1. Together, our findings reveal a tumour suppressor function of SIAH1 and provide evidence showing that the SIAH1-RPS3-NF-κB axis may act as an appealing strategy for tackling treatment resistance in EOC.

Keywords

EOC; NF-κB; RPS3; SIAH1; chemoresistance.

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