Journal
JOURNAL OF HEPATOCELLULAR CARCINOMA
Volume 8, Issue -, Pages 759-771Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/JHC.S315634
Keywords
SERPINA11; HCC; metastasis; uPA; ERK
Categories
Funding
- National Natural Science Foundation of China [81802335, 81872007, 81772554]
- Natural Science Foundation of Guangdong Province [2018A030310175, 2018A030313034, 2021A1515010589]
- Young Doctoral Plan of Guangzhou Medical University [2016C42]
- Young Doctoral Plan of Guangdong Health Commission [B2018059]
- General Guidance Plan ofGuangzhou Health commission [20181A010062]
- Young Talent Teachers Plan of Sun Yatsen University [15ykpy33]
- National Basic Research Program of China [2012CB967001]
- China National Key SciTech Special Project of Infectious Diseases [2018ZX10723204006005]
- Shenzhen Peacock team Project [KQDT2015033117210153]
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The study identified SERPINA11 as a novel tumor suppressor in HCC, with the ability to inhibit cell growth, migration, and tumor metastasis. It has potential as a biomarker and intervention point for new therapeutic strategies in HCC.
Purpose: By using integrative RNA sequencing analysis, we identified a novel tumor suppressor, serpin family A member 11 (SERPINA11), which is a serine proteinase inhibitor that belongs to the serpin superfamily. However, the function of SERPINA11 in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the role and molecular mechanism of SERPINA11 in HCC. Methods: Gene expression patterns of SERPINA11 were analyzed in tissue samples of HCC patients by qRT-PCR. In vitro and in vivo experiments were performed to characterize the function and molecular mechanism of SERPINA11 in the tumor metastasis capacity. Results: SERPINA11 was downregulated in approximately 50% of HCC and significantly associated with metastasis and poor outcome of patients. Functional study demonstrated that SERPINA11 could inhibit cell growth, cell migration and tumor metastasis. Mechanistic investigations suggested that SERPINA11 accelerated urokinase-type plasminogen activator (uPA) degradation to suppress extracellular signal-regulated kinase (ERK1/2) phosphorylation, and thereby subdued metastatic capabilities of HCC cells. Conclusion: SERPINA11 plays an important tumor suppressive role in HCC, with possible use as a biomarker and an intervention point for new therapeutic strategies.
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