MicroRNA-mRNA regulatory network study and apoptosis analysis on bone marrow endothelial cells induced by liver...

As important components of bone marrow microenvironment, bone marrow endothelial cells (BMECs) have important roles in regulating haematopoietic functions of the bone marrow. In preliminary study, we found the humoral inhibitor in liver cirrhosis (LC) could lead to ultrastructure alterations of the bone marrow endothelium. The present study aimed to investigate functional changes occurred in BMECs during LC.

A multi-step approach combining microarray microRNA (miRNA) and mRNA expression profiling and bioinformatics analysis was used to generate a specific miRNA-mRNA regulatory network in BMECs treated with supplemented medium with 20% pooled sera from 26 patients with LC or 10 healthy volunteers as a control group for 48h.

A total of 372 differentially expressed miRNAs and 1872 differentially expressed mRNAs were identified by miRNA and mRNA microarray, respectively. Twenty-one dysregulated miRNAs and their 23 dysregulated target mRNAs confirmed by experiment (31 miRNA-mRNA interactions) were screened based on databases miRecords and miRTarBase. Bioinformatics analysis revealed that the functions of these miRNA-mRNA interactions were involved in the positive regulation of apoptosis, negative regulation of cell proliferation, cell cycle arrest and so on. The results of flow cytometry analysis showed that the LC serum treated-BMECs had a higher apoptosis percentage (17.57±1.84%) compared to the control group (10.2±1.55%). (P<0.05) CONCLUSIONS: Thirty-one miRNA-mRNA pairs combined with 21 dysregulated miRNAs and their 23 target mRNAs identified by the multi-step approach are involved in BMECs treated with LC serum. The results indicated that LC serum-induced apoptosis in BMECs were regulated by a complicated miRNA-mRNA regulatory network.