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Published on: February 6, 2015
Downregulation of SSR2 Enhances Hepatocellular Carcinoma Cisplatin Sensitivity via the Hippo Pathway
Rong Ye1, Ling Yin2, Yilong Ge3
1Department of General Surgery III, The First Affiliated Hospital of Gannan Medical University, 341000 Ganzhou, Jiangxi, China.
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 in vivo 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.
Insights
Signal sequence receptor subunit 2 (SSR2) upregulation promotes hepatocellular carcinoma (HCC) progression and chemoresistance. Targeting the SSR2/Hippo axis may enhance chemotherapy effectiveness in HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Hepatocellular carcinoma (HCC) chemoresistance limits patient survival.
- Novel therapeutic targets are needed to overcome HCC chemotherapy resistance.
Purpose of the Study:
- To investigate the role of Signal sequence receptor subunit 2 (SSR2) in HCC.
- To explore SSR2 as a potential therapeutic target for enhancing HCC chemotherapy.
Main Methods:
- Quantitative real-time polymerase chain reaction (qPCR) and Western blotting for SSR2 expression.
- Assays for cell proliferation, apoptosis, and anchorage-independent growth.
- In vivo animal models and molecular mechanism studies (luciferase reporter assays).
Main Results:
- SSR2 is upregulated in HCC and linked to poor patient survival.
- Downregulation of SSR2 increases HCC sensitivity to Cisplatin (DDP).
- SSR2 inhibits YAP phosphorylation, promoting Hippo pathway gene transcription.
Conclusions:
- SSR2 plays a critical role in HCC progression through the Hippo pathway.
- Targeting the SSR2/Hippo axis is a potential strategy to overcome DDP resistance in HCC.
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