SSR2 的下调通过 Hippo 通路增强肝癌对顺铂的敏感性。

Downregulation of SSR2 Enhances Hepatocellular Carcinoma Cisplatin Sensitivity via the Hippo Pathway.

机构信息

Department of General Surgery III, The First Affiliated Hospital of Gannan Medical University, 341000 Ganzhou, Jiangxi, China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Gannan Medical University, 341000 Ganzhou, Jiangxi, China.

出版信息

Front Biosci (Landmark Ed). 2024 Aug 21;29(8):299. doi: 10.31083/j.fbl2908299.

DOI:10.31083/j.fbl2908299

PMID:39206890

Abstract

BACKGROUND

Chemotherapy resistance is an obstacle to promoting the survival of patients with hepatocellular carcinoma (HCC). Thus, finding promising therapeutic targets to enhance HCC chemotherapy is necessary.

METHODS

Signal sequence receptor subunit (SSR2) expression analysis was performed using quantitative real time polymerase chain reaction (qPCR) and Western blotting assays. Colony formation, apoptosis, anchorage-independent growth assay, and animal models were used to investigate the effect of SSR2 expression on the resistance of HCC cells to Cisplatin (DDP). Western blotting and luciferase reporter gene techniques were used to explore the molecular mechanism of SSR2 on the resistance of HCC cells to DDP.

RESULTS

We found that the SSR2 is upregulated in HCC and associated with poor survival. Further analysis showed that the downregulation of SSR2 increased the sensitivity of HCC to DDP. Mechanically, SSR2 inhibited the Yes-associated protein (YAP) phosphorylation and promoted the transcription of Hippo signaling downstream genes. Finally, the Hippo pathway inhibitor can suppress colony formation and tumorigenesis arising from SSR2 upregulation.

CONCLUSIONS

Our study shows that SSR2 is important in HCC progression via the Hippo pathway. Thus, targeting the SSR2/Hippo axis might be a potential strategy for overcoming HCC resistance to DDP.

摘要

背景

化疗耐药性是促进肝细胞癌（HCC）患者生存的障碍。因此，寻找有前途的治疗靶点以增强 HCC 化疗是必要的。

方法

使用定量实时聚合酶链反应（qPCR）和 Western blot 分析检测信号序列受体亚基（SSR2）的表达。通过集落形成、细胞凋亡、非依赖性生长测定和动物模型研究 SSR2 表达对 HCC 细胞对顺铂（DDP）耐药性的影响。Western blot 和荧光素酶报告基因技术用于探讨 SSR2 对 HCC 细胞对 DDP 耐药性的分子机制。

结果

我们发现 SSR2 在 HCC 中上调，并与不良预后相关。进一步的分析表明，SSR2 的下调增加了 HCC 对 DDP 的敏感性。在机制上，SSR2 抑制了 Yes 相关蛋白（YAP）的磷酸化，并促进了 Hippo 信号下游基因的转录。最后，Hippo 通路抑制剂可以抑制 SSR2 上调引起的集落形成和肿瘤发生。