Reconstruction of pathway modification induced by nicotinamide using multi-omic network analyses in triple negative breast cancer.

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.

• Authors: Ji Young Kim, Hyebin Lee, Jongmin Woo, Wang Yue, Kwangsoo Kim, Seongmin Choi, Ja-June Jang, Youngsoo Kim, In Ae Park, Dohyun Han, Han Suk Ryu
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 3466 (06 14 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28615672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Niacinamide

Topics

• Computational Biology (methods)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks (drug effects)
• Genomics (methods)
• Humans
• Models, Biological
• Molecular Sequence Annotation
• Niacinamide (pharmacology)
• Proteomics (methods)
• Signal Transduction (drug effects)
• Triple Negative Breast Neoplasms (genetics, metabolism)