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LNX1 Contributes to Cell Cycle Progression and Cisplatin Resistance
Minsu Jang1, Rackhyun Park1, Yea-In Park1
1Division of Biological Science and Technology, Yonsei University, Wonju 26493, Korea.
Abstract:
The ligand of numb-protein X1 (LNX1) acts as a proto-oncogene by inhibiting p53 stability; however, the regulation of LNX1 expression has not been investigated. In this study, we screened chemicals to identify factors that potentially regulate LNX1 expression. We found that LNX1 expression levels were decreased by DNA damage, including that by cisplatin. Upon treatment with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA), LNX1 expression levels increased. In addition, cell-cycle progression increased upon LNX1 expression; the levels of S and G2/M populations were correlated with LNX1 expression. Moreover, in CRISPR-Cas9-mediated LNX1 knockout cells, we observed a delay in cell-cycle progression and a downregulation of genes encoding the cell-cycle markers cyclin D1 and cyclin E1. Finally, the upregulation of LNX1-activated cell-cycle progression and increased resistance to cisplatin-mediated cell death. Taken together, these results suggest that LNX1 contributes to cell-cycle progression and cisplatin resistance.
Insights
Ligand of numb-protein X1 (LNX1) promotes cell cycle progression and cisplatin resistance. LNX1 expression is regulated by DNA damage and inflammatory stimuli, impacting cell division and survival.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ligand of numb-protein X1 (LNX1) functions as a proto-oncogene by inhibiting p53 stability.
- The regulatory mechanisms governing LNX1 expression remain largely uninvestigated.
Purpose of the Study:
- To identify factors that regulate LNX1 expression.
- To elucidate the role of LNX1 in cell-cycle progression and chemoresistance.
Main Methods:
- Chemical screening to identify LNX1 expression regulators.
- Treatment with DNA-damaging agents (cisplatin), lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA).
- CRISPR-Cas9 gene editing to create LNX1 knockout cells.
- Cell-cycle analysis (flow cytometry) and gene expression analysis.
Main Results:
- LNX1 expression decreased upon DNA damage (cisplatin) and increased with LPS and PMA treatment.
- LNX1 expression correlated with increased S and G2/M cell-cycle populations.
- LNX1 knockout cells exhibited delayed cell-cycle progression and downregulated cyclin D1 and cyclin E1.
- Upregulation of LNX1 enhanced cell-cycle progression and increased resistance to cisplatin-induced cell death.
Conclusions:
- LNX1 plays a significant role in promoting cell-cycle progression.
- LNX1 contributes to cellular resistance against cisplatin-mediated apoptosis.
- LNX1 expression is modulated by DNA damage and inflammatory signals, suggesting its involvement in cancer development and progression.
Related Concept Videos
DNA Damage can Stall the Cell Cycle
Negative Regulator Molecules
Inhibition of Cdk Activity
The Intrinsic Apoptotic Pathway
Abnormal Proliferation
Treatment Resistant Cancers

