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

Chen, Lu; Gao, Wujiang; Sha, Chunli; Yang, Meiling; Lin, Li; Li, Taoqiong; Wei, Hong; Chen, Qi; Xing, Jie; Zhang, Mengxue; Zhao, Shijie; Xu, Wenlin; Li, Yuefeng; Zhu, Xiaolan

doi:10.18632/aging.204211

Cited by 8 publications

(1 citation statement)

References 61 publications

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“…We identified that the E3 ubiquitin ligase SIAH1 is responsible for the degradation of HMGCR. SIAH1 has been reported to act as a tumor suppressor during tumorigeneses, such as liver, ovarian, and breast [ 29 , 30 ]. In addition, SIAH1 has been demonstrated to regulate multidrug resistance 1 (MDR1)/P-glycoprotein-mediated drug resistance in cancer [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

SIAH1 ubiquitination-modified HMGCR inhibits lung cancer progression and promotes drug sensitivity through cholesterol synthesis

Yuan

Cheng

et al. 2023

Cancer Cell Int

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Backgrounds Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide. Deep understanding of chemoresistance will lead to remarkable progress in lung cancer treatment strategy. Cholesterol accumulation was associated with cisplatin resistance in lung cancer treatment. And we found the degree of cisplatin resistance was correlated with the expression of the cholesterol synthesis HMGCR. Methods We analyzed a group of 42 lung cancer patients who received cisplatin treatment after lung resection surgery. The expression of HMGCR and its correlation with cholesterol in lung cancer cell lines were determined by qRT-PCR and ELISA analyses. We focus on the function and mechanism of HMGCR in lung cancer and reveal that knockdown of HMGCR expression inhibits the proliferation, colony formation, and migration of lung cancer cell lines in vitro or in vivo and dramatically enhances the efficacy of cisplatin. Results Through mechanism studies, we illustrate that SIAH1, an E3 ubiquitin-protein ligase, ubiquitination modifies HMGCR and inhibits efflux protein activity via regulating cholesterol synthesis. In vivo experiments showed that SIAH1 overexpression or using HMGCR knockdown retard tumor growth and enhanced the efficacy of cisplatin. In summary, HMGCR affects cholesterol metabolism by regulating key enzymes in cholesterol synthesis, thereby reducing drug sensitivity. Conclusion This study indicates that lung cancer patients with lower HMGCR levels may lead to a better prognosis and provide a potential treatment by SIAH1 overexpression for lung cancer patients with cisplatin resistance.

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Section: Discussionmentioning

confidence: 99%

SIAH1 ubiquitination-modified HMGCR inhibits lung cancer progression and promotes drug sensitivity through cholesterol synthesis

Yuan

Cheng

et al. 2023

Cancer Cell Int

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Ribosomal rodeo: wrangling translational machinery in gynecologic tumors

Filipek,

Penzo

2024

Cancer Metastasis Rev

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Gynecologic cancers are a significant cause of morbidity and mortality among women worldwide. Despite advancements in diagnosis and treatment, the molecular mechanisms underlying the development and progression of these cancers remain poorly understood. Recent studies have implicated translational machinery (ribosomal proteins (RPs) and translation factors (TFs)) as potential drivers of oncogenic processes in various cancer types, including gynecologic cancers. RPs are essential components of the ribosome, which is responsible for protein synthesis. In this review paper, we aim to explore the role of translational machinery in gynecologic cancers. Specifically, we will investigate the potential mechanisms by which these components contribute to the oncogenic processes in these cancers and evaluate the feasibility of targeting RPs as a potential therapeutic strategy. By doing so, we hope to provide a broader view of the molecular pathogenesis of gynecologic cancers and highlight their potential as novel therapeutic targets for the management of these challenging diseases.

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Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy

Guo,

Wei,

Zhang

et al. 2024

Genes & Diseases

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

Cited by 8 publications

References 61 publications

SIAH1 ubiquitination-modified HMGCR inhibits lung cancer progression and promotes drug sensitivity through cholesterol synthesis

SIAH1 ubiquitination-modified HMGCR inhibits lung cancer progression and promotes drug sensitivity through cholesterol synthesis

Ribosomal rodeo: wrangling translational machinery in gynecologic tumors

Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy

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