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Published on: July 20, 2019
Reconstruction of pathway modification induced by nicotinamide using multi-omic network analyses in triple negative
Ji Young Kim1, Hyebin Lee2, Jongmin Woo3
1Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Abstract:
Triple negative breast cancer (TNBC) is characterized by an aggressive biological behavior in the absence of a specific target agent. Nicotinamide has recently been proven to be a novel therapeutic agent for skin tumors in an ONTRAC trial. We performed combinatory transcriptomic and in-depth proteomic analyses to characterize the network of molecular interactions in TNBC cells treated with nicotinamide. The multi-omic profiles revealed that nicotinamide drives significant functional alterations related to major cellular pathways, including the cell cycle, DNA replication, apoptosis and DNA damage repair. We further elaborated the global interaction networks of molecular events via nicotinamide-inducible expression changes at the mRNA and functional protein levels. This approach indicated that nicotinamide treatment rewires interaction networks toward dysfunction in DNA damage repair and away from a pro-growth state in TNBC. To our knowledge, the high-resolution network interactions identified in the present study provide the first evidence to comprehensively support the hypothesis of nicotinamide as a novel therapeutic agent in TNBC.
Insights
Nicotinamide shows promise as a novel therapeutic agent for triple negative breast cancer (TNBC). This study reveals it alters key cellular pathways, disrupting DNA repair and growth in TNBC cells.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Triple negative breast cancer (TNBC) presents an aggressive clinical challenge due to the lack of targeted therapies.
- Nicotinamide has demonstrated therapeutic potential in skin tumors.
Purpose of the Study:
- To investigate the molecular mechanisms of nicotinamide in triple negative breast cancer cells.
- To characterize the network of molecular interactions affected by nicotinamide treatment in TNBC.
Main Methods:
- Combined transcriptomic and proteomic analyses were employed to study TNBC cells treated with nicotinamide.
- Global molecular interaction networks were mapped based on mRNA and protein expression changes.
Main Results:
- Nicotinamide induced significant functional alterations in cell cycle, DNA replication, apoptosis, and DNA damage repair pathways.
- Treatment with nicotinamide reprogrammed molecular networks, impairing DNA damage repair and reducing proliferation in TNBC.
- High-resolution network interactions provide comprehensive support for nicotinamide's efficacy.
Conclusions:
- Nicotinamide exhibits potential as a novel therapeutic agent for triple negative breast cancer.
- The study provides mechanistic insights into nicotinamide's anti-cancer effects by modulating critical cellular pathways and interaction networks.
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