Tumor metastasis and chemoresistance are the main causes of treatment failure and high mortality in hepatocellular carcinoma (HCC). Therefore, it is critical to clarify the biological action and potential mechanisms in HCC cells to develop novel therapeutics. The regulator of chromosome condensation 2 (RCC2), a component of the chromosomal passenger complex, was shown to have important roles in tumor development and radio-chemotherapy resistance. However, its role in the aggressive phenotypes and cisplatin (DDP)-resistance of HCC is not known. Therefore, this study aimed to investigate the role of RCC2 in HCC pathogenesis. Interestingly, we found that RCC2 was upregulated in HCC patient specimens and HCC cell lines and was correlated with the pathological grade of HCC. To evaluate the function of RCC2 in HCC cell, lentivirus vector-based shRNAs were transfected into HCC cells. Silencing RCC2 inhibited the HCC cell proliferation, migration, invasion, and increased the apoptosis rate upon DDP treatment. Further analysis showed that RCC2-mediated downregulation of the expression of survival proteins occurred via the AKT and Bcl2 pathways. Our results suggest that RCC2 might act as an oncogenic protein promoting metastatic behaviors and cisplatin resistance in HCC cells, and thereby could be a potential prognostic biomarker and therapeutic target for HCC.

中文翻译：

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RCC2 有助于肝细胞癌中的肿瘤侵袭和对顺铂的化疗耐药。


肿瘤转移和化疗耐药是肝细胞癌（HCC）治疗失败和高死亡率的主要原因。因此，阐明 HCC 细胞的生物学作用和潜在机制对于开发新的治疗方法至关重要。 2 号染色体浓缩调节因子 (RCC2) 是染色体过客复合体的一个组成部分，已被证明在肿瘤发展和放化疗耐药性中具有重要作用。然而，其在 HCC 侵袭性表型和顺铂 (DDP) 耐药性中的作用尚不清楚。因此，本研究旨在探讨RCC2在HCC发病机制中的作用。有趣的是，我们发现RCC2在HCC患者标本和HCC细胞系中表达上调，并且与HCC的病理分级相关。为了评估 RCC2 在 HCC 细胞中的功能，将基于慢病毒载体的 shRNA 转染到 HCC 细胞中。沉默RCC2可抑制HCC细胞的增殖、迁移、侵袭，并增加DDP处理后的凋亡率。进一步分析表明，RCC2 介导的生存蛋白表达下调是通过 AKT 和 Bcl2 途径发生的。我们的结果表明，RCC2 可能作为一种致癌蛋白，促进 HCC 细胞的转移行为和顺铂耐药，从而可能成为 HCC 的潜在预后生物标志物和治疗靶点。