A multi-omits analysis of the regulatory changes induced by miR-223 in a monocyte/macrophage cell line

作者：M'baya Moutoula Eleonore; Louvet Loic; Molinie Roland; Guerrera Ida Chiara; Cerutti Catherine; Fourdinier Ophelie; Nourry Virginie; Gutierrez Laurent; Morliere Patrice; Mesnard Francois; Massy Ziad A; Metzinger Le Meuth Valerie^*; Metzinger Laurent^*

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2018, 1864(8): 2664-2678.

DOI：10.1016/j.bbadis.2018.05.010

• Cell death
• Macrophage
• miR-223
• Multi-omics
• NF-kappa B
• Osteoclastogenesis

We used a multi-omics approach to study the impact of over-expression and inhibition of the microRNA miR-223, a pleiotropic regulator of metabolic-related disease, in a monocyte-macrophage cell line. We analyzed the levels of proteins, mRNAs, and metabolites in order to identify candidate molecules involved in miR-223 regulation, to determine disease biomarkers and potential therapeutic targets. Microarray-based transcriptomics evidenced a change in 120 genes that were linked predominantly to histone acetylation, bone remodeling and RNA regulation. In addition, 30 out the 120 genes encoded long noncoding RNAs. The nanoLC-MS/MS experiment revealed that 52 proteins were significantly altered when comparing treatments. Gene Ontology analyses evidenced association with cell death, splicing and stability of mRNAs, bone remodeling and metabolism. Among targets, miR-223 alteration changed the expression of CARM-1, Ube2g2, Cactin and Ndufaf6 during macrophage differentiation and osteoclastogenesis, indicating that these genes are potential biomarkers of these processes. The most important discriminant metabolites found in the metabolomics study were found to be hydrophilic amino acids, carboxylic acids linked to metabolism and pyrimidine nucleotides, indicating that changes in miR-223 expression alter the metabolic profile of cells, and may affect their apoptotic and proliferative state.

• 出版日期2018-8