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Updated: Nov 22, 2025
Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells
Published on: June 13, 2018
iTRAQ-based proteomic analysis of the molecular mechanisms and downstream effects of fatty acid synthase in
Dahua Fu1, Shuochuan Liu2, Jiaming Liu3,4
1Department of Pharmacy, Zhangzhou health vocational college, Zhangzhou, China.
Background:
Fatty acid synthase (FASN) is a lipogenic enzyme that participates in tumor progression. We previously showed that FASN is dysregulated in OS malignancy, but the molecular mechanism(s) of these effects remained unclear.
Methods:
We examined differentially expressed proteins (DEPs) in FASN-silenced osteosarcoma 143B cells and their parental cells by isobaric tags for relative and absolute quantitation (iTRAQ). Differentially expressed proteins were classified using GO and KEGG analysis. The association between FASN and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) was confirmed using qPCR, Western blot, and immunohistochemistry. The function of HNRNPA1 in osteosarcoma was determined using CCK-8, colony formation, wound healing, transwell migration, and invasion assays.
Results:
Among the 4971 identified proteins, 567 DEPs (325 upregulated and 242 downregulated) were identified. The top 10 upregulated proteins comprised HIST1H2AB, INA, INTS5, MTCH2, EIF1, MAPK1IP1L, PXK, RPS27, PM20D2, and ZNF800, while the top 10 downregulated proteins comprised NDRG1, CNTLN, STON2, GDF7, HECTD3, HBB, TPM1, PPP4R4, PTTG1IP, and PLCB3. Bioinformatic analysis indicated that the DEPs were related to cellular processes, metabolic processes, biological regulation, binding, and catalytic activity. HNRNPA1 was dysregulated in FASN-silenced 143B and HOS cells. qPCR, Western blot, and immunohistochemistry showed that FASN expression positively correlates with HNRNPA1 expression. Further studies indicated that HNRNPA1 correlates with OS diagnosis and prognosis. And HNRNPA1 silence inhibits the proliferation, migration, and invasion in OS cells.
Conclusion:
HNRNPA1 acts as targets downstream of FASN and potential biomarker and oncogene in OS.
Insights
Fatty acid synthase (FASN) dysregulation in osteosarcoma (OS) is linked to heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1). HNRNPA1 acts as a downstream target of FASN, promoting OS progression and serving as a potential biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Fatty acid synthase (FASN) is a lipogenic enzyme implicated in tumor progression.
- FASN dysregulation is observed in osteosarcoma (OS) malignancy, but its underlying molecular mechanisms are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms by which FASN influences osteosarcoma progression.
- To identify downstream targets of FASN and their role in OS development and prognosis.
Main Methods:
- Differential protein expression analysis using isobaric tags for relative and absolute quantitation (iTRAQ) in FASN-silenced osteosarcoma cells.
- Bioinformatic analysis (Gene Ontology and KEGG) to classify differentially expressed proteins.
- Validation of FASN and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) association using qPCR, Western blot, and immunohistochemistry.
- Functional assays (CCK-8, colony formation, migration, invasion) to assess HNRNPA1's role in OS.
Main Results:
- 567 differentially expressed proteins were identified in FASN-silenced cells, with 325 upregulated and 242 downregulated.
- Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) was found to be dysregulated and positively correlated with FASN expression in OS cells.
- HNRNPA1 expression correlated with OS diagnosis and prognosis, and its silencing inhibited OS cell proliferation, migration, and invasion.
Conclusions:
- Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is a downstream target of Fatty acid synthase (FASN) in osteosarcoma.
- HNRNPA1 functions as an oncogene and a potential biomarker in osteosarcoma progression.
