RNF2 promotes chondrosarcoma progression by regulating ubiquitination and degradation of CBX7.

IF 6 3区医学 Q1 CELL BIOLOGY Cancer & Metabolism Pub Date : 2024-10-25 DOI:10.1186/s40170-024-00359-x

Yue Wu, Zheng Huang, Ping Luo, Zhong Xiang, Meng Zhang, Zhiwu Chen, Yalu Zhou, Jiameng Li

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Abstract

Objective: Chondrosarcoma (CHS) is resistant to conventional chemotherapy and radiotherapy and currently lacks effective treatment options when in advanced stages. Accordingly, this research investigated the mechanism of RNF2/CBX7 in CHS to drive the development of molecularly targeted drugs for CHS.

Methods: RNF2 and CBX7 levels were detected in CHS cells and tissues. RNF2 and CBX7 expression was modulated through cell transfection to examine their effects on cell proliferation, apoptosis, migration, and angiogenesis. The correlation between RNF2 and CBX7 levels was determined, and the ubiquitination level of CBX7 was tested. Protein synthesis was blocked in RNF2-knockdown/overexpressing cells with CHX to assess the effect of RNF2 on CBX7 stability. JJ012 cells transfected with LV-sh-RNF2 were subcutaneously injected into nu/nu nude mice to ascertain the action of RNF2 in the growth and metastasis of CHS.

Results: RNF2 was highly expressed in CHS cells and tissues. RNF2 knockdown curbed CHS cell proliferation, migration, and angiogenesis while promoting apoptosis. RNF2 knockdown in JJ012 cells upregulated CBX7 protein levels and reduced CBX7 ubiquitination, whilst RNF2 had no effect on CBX7 mRNA expression. CBX7 knockdown partially nullified the repressing effects of RNF2 knockdown on CHS cell proliferation, migration, and angiogenesis, and CBX7 overexpression partially abolished the promotional effects of RNF2 overexpression. LV-sh-RNF2 prominently restricted tumor growth and weight and declined lung metastatic nodules and Ki-67-positive cells in mice.

Conclusion: RNF2 fosters CHS progression by elevating CBX7 degradation via the ubiquitination pathway.

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RNF2 通过调控 CBX7 的泛素化和降解促进软骨肉瘤的发展。

目的：软骨肉瘤（CHS软骨肉瘤（Chondrosarcoma，CHS）对传统化疗和放疗具有耐药性，目前在晚期阶段缺乏有效的治疗方案。因此，本研究探讨了 RNF2/CBX7 在 CHS 中的作用机制，以推动 CHS 分子靶向药物的开发：方法：检测CHS细胞和组织中的RNF2和CBX7水平。方法：检测 CHS 细胞和组织中 RNF2 和 CBX7 的水平，通过细胞转染调节 RNF2 和 CBX7 的表达，研究它们对细胞增殖、凋亡、迁移和血管生成的影响。测定了 RNF2 和 CBX7 水平之间的相关性，并检测了 CBX7 的泛素化水平。用 CHX 阻断 RNF2 敲除/高表达细胞的蛋白质合成，以评估 RNF2 对 CBX7 稳定性的影响。将转染了LV-sh-RNF2的JJ012细胞皮下注射到nu/nu裸鼠体内，以确定RNF2在CHS生长和转移中的作用：结果：RNF2在CHS细胞和组织中高表达。结果：RNF2在CHS细胞和组织中高表达，敲除RNF2可抑制CHS细胞的增殖、迁移和血管生成，同时促进细胞凋亡。在 JJ012 细胞中敲除 RNF2 会上调 CBX7 蛋白水平并减少 CBX7 泛素化，而 RNF2 对 CBX7 mRNA 的表达没有影响。CBX7 基因敲除部分抵消了 RNF2 基因敲除对 CHS 细胞增殖、迁移和血管生成的抑制作用，而 CBX7 基因过表达则部分抵消了 RNF2 基因过表达的促进作用。LV-sh-RNF2显著限制了肿瘤的生长和重量，并减少了小鼠肺转移结节和Ki-67阳性细胞：结论：RNF2通过泛素化途径促进CBX7降解，从而促进CHS进展。

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来源期刊

Cancer & Metabolism Multiple-

自引率

1.70%

发文量

审稿时长

14 weeks

期刊介绍： Cancer & Metabolism welcomes studies on all aspects of the relationship between cancer and metabolism, including: -Molecular biology and genetics of cancer metabolism -Whole-body metabolism, including diabetes and obesity, in relation to cancer -Metabolomics in relation to cancer; -Metabolism-based imaging -Preclinical and clinical studies of metabolism-related cancer therapies.