Back to Search
Start Over
CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.
CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.
- Source :
-
Molecular cancer [Mol Cancer] 2024 May 28; Vol. 23 (1), pp. 113. Date of Electronic Publication: 2024 May 28. - Publication Year :
- 2024
-
Abstract
- Background: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa&#95;circ&#95;0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development.<br />Methods: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms.<br />Results: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib.<br />Conclusion: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Humans
Male
Mice
Cell Line, Tumor
Cell Movement genetics
Disease Progression
Xenograft Model Antitumor Assays
Basic Helix-Loop-Helix Transcription Factors metabolism
Basic Helix-Loop-Helix Transcription Factors genetics
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular pathology
Carcinoma, Hepatocellular metabolism
Cell Proliferation
Ferroptosis genetics
Gene Expression Regulation, Neoplastic
Liver Neoplasms genetics
Liver Neoplasms pathology
Liver Neoplasms metabolism
MicroRNAs genetics
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
RNA, Circular genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4598
- Volume :
- 23
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cancer
- Publication Type :
- Academic Journal
- Accession number :
- 38802795
- Full Text :
- https://doi.org/10.1186/s12943-024-02030-x