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CXCL5/NF-κB Pathway as a Therapeutic Target in Hepatocellular Carcinoma Treatment
Xingqing Jia1, Shuangqin Wei1, Wujun Xiong2
1Department of Hepatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 201399, China.
Background:
Hepatocellular carcinoma (HCC) is a common malignant cancer worldwide. CXCL5 has a role in inhibiting cell viability and metastasis in many tumors. In the present study, we investigated the role of CXCL5 in HCC and explored the underlying mechanism. Material and Methods. RT-qPCR and western blot were performed to evaluate the mRNA and protein levels of CXCL5. CCK-8 and transwell assay were applied to measure the proliferative and invasive abilities. Meanwhile, the Kaplan-Meier method was used to assess the survival of HCC patients.
Results:
CXCL5 was upregulated in HCC tissues, which predicted a shorter overall survival in HCC. CXCL5 was a target gene of miR-577, and its expression was mediated by miR-577 in HCC. Knockdown of CXCL5 suppressed HuH-7 cell proliferation, invasion, and EMT and inhibited the NF-κB signaling pathway in cells. Moreover, knockdown of CXCL5 inhibited the xenograft growth of HuH-7 cells.
Conclusion:
Overexpression of CXCL5 predicts poor prognosis in HCC patients. Knockdown of CXCL5 inhibits cell proliferation and invasion through the NF-κB signaling pathway in HCC. The newly identified role of the CXCL5/miR-577/NF-κB axis provides novel insights into the targeted therapy of HCC.
Insights
High CXCL5 levels in hepatocellular carcinoma (HCC) predict poor patient survival. Reducing CXCL5 inhibits cancer growth and spread by affecting the NF-κB pathway, offering new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hepatocellular carcinoma (HCC) is a prevalent global malignancy.
- Chemokine (C-X-C motif) ligand 5 (CXCL5) exhibits inhibitory roles in various tumor types.
- The specific function and mechanism of CXCL5 in HCC remain to be fully elucidated.
Purpose of the Study:
- To investigate the role and underlying mechanism of CXCL5 in hepatocellular carcinoma.
- To explore the prognostic significance of CXCL5 in HCC patients.
- To identify potential therapeutic targets within the CXCL5 pathway.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blot to assess CXCL5 mRNA and protein expression.
- Cell Counting Kit-8 (CCK-8) and Transwell assays to evaluate cell proliferation and invasion.
- Kaplan-Meier survival analysis to correlate CXCL5 expression with patient prognosis.
Main Results:
- CXCL5 was found to be upregulated in HCC tissues, correlating with shorter overall survival.
- CXCL5 was identified as a target gene of miR-577, with its expression regulated by miR-577 in HCC.
- Knockdown of CXCL5 inhibited proliferation, invasion, and epithelial-mesenchymal transition (EMT) in HuH-7 cells, alongside suppressing the NF-κB signaling pathway and xenograft tumor growth.
Conclusions:
- Overexpression of CXCL5 serves as a predictor of poor prognosis in HCC.
- Reducing CXCL5 levels inhibits HCC cell proliferation and invasion via the NF-κB signaling pathway.
- The identified CXCL5/miR-577/NF-κB axis presents novel therapeutic strategies for HCC treatment.
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