Integrative proteomic and microRNA analysis of the priming phase during rat liver regeneration

• High-throughput sequencing of miRNA expression profiles in rat LR was performed.
• iTRAQ-based proteomics analysis of the priming phase of rat LR was conducted.
• 6 miRNAs were found to regulate the priming phase of rat LR by integrative analysis.
• A functional molecular network was built in the priming phase of rat LR.

The partial hepatectomy (PH) model provides an effective medium for study of liver regeneration (LR). Considering that LR is regulated by microRNAs (miRNAs), investigation of the regulatory role of miRNAs is critical for revealing how regenerative processes are initiated and controlled. Using high-throughput sequencing technology, we examined miRNA expression profiles of the regenerating rat liver after PH, and found that 23 miRNAs were related to rat LR. Among them, several miRNAs were significantly altered at 2 h and 6 h after PH, corresponding to the priming phase of LR. Furthermore, we examined the protein profiles in the regenerating rat liver at 2 h and 6 h after PH by iTRAQ coupled with LC-MS/MS, and found that 278 proteins were significantly changed. Subsequently, an integrative proteomic and microRNA analysis by Ingenuity Pathway Analysis 9.0 (IPA) software showed that miR-125a, miR-143, miR-150, miR-181c, miR-182, miR-183, miR-199a, miR-429 regulated the priming phase of rat LR by modulating the expression of proteins involved in networks critical for cell apoptosis, cell survival, cell cycle, inflammatory response, metabolism, etc. Thus, our studies provide novel evidence for a functional molecular network populated by the down-regulated targets of the up-regulated miRNAs in the priming phase of rat LR.