Associative Analysis of lncRNA/circRNA-miRNA-mRNA Expression Profiles in Iron-Overloaded HT-1080 Fibrosarcoma Cells.

Area of Science:

• Cell Biology
• Molecular Biology
• Genomics

Background:

• Iron overload disrupts cellular homeostasis and induces ferroptosis via altered iron metabolism.
• Non-coding RNAs (ncRNAs) are crucial regulators of biological processes, with potential as therapeutic targets and biomarkers.
• The role of ncRNAs, especially competitive endogenous RNAs (ceRNAs), in iron overload remains underexplored.

Purpose of the Study:

• To characterize the ceRNA network in cells experiencing iron overload.
• To identify ncRNAs involved in regulating ferroptosis pathways.
• To explore potential ncRNA-based therapeutic strategies for iron overload.

Main Methods:

• Whole-transcriptome sequencing was performed on ferric ammonium citrate (FAC)-induced iron-overloaded HT-1080 fibrosarcoma cells.
• Differential gene expression analysis identified significant changes in mRNAs, lncRNAs, and circRNAs.
• KEGG pathway enrichment analysis and ceRNA network construction were utilized to understand regulatory mechanisms.

Main Results:

• 208 mRNAs, 83 lncRNAs, and 170 circRNAs were differentially expressed in iron-overloaded cells.
• KEGG analysis highlighted disruptions in vitamin B6 metabolism and lysine degradation pathways.
• The ceRNA network revealed lncRNA/circRNA regulation of ferroptosis genes, with LINC-PINT-232 identified as a key regulator of FTH and SQSTM1.

Conclusions:

• This study provides a preliminary transcriptomic landscape of ncRNA regulation in iron overload-induced ferroptosis.
• Findings suggest ncRNAs play a significant role in modulating iron metabolism and ferroptosis.
• The identified ncRNAs, particularly LINC-PINT-232, offer potential targets for future research and therapeutic interventions in iron overload conditions.