Abstract. Toll-like receptors (TLRs) are expressed in human bone marrow-derived mesenchymal stromal cells (BM-MScs). The activation of TLRs is important in the proliferation, differ entiation, migration and hematopoiesis-supporting functions of BM-MScs. MicroRNAs (miRNAs) are involved in various bio

Toll-like receptors (TLRs) are expressed in human bone marrow-derived mesenchymal stromal cells (BM-MScs). The activation of TLRs is important in the proliferation, differ entiation, migration and hematopoiesis-supporting functions of BM-MScs. MicroRNAs (miRNAs) are involved in various biological functions by mediating mRNA degradation or inhibiting the translation of target genes. Our previous study confirmed that TLRs regulate the migration ability of BM‐MSCs. It was also identified that multiple miRNAs were regulated by TLRs. In view of this, it was hypothesized that TLR-regulated miRNAs may be important in regulating the migration of BM-MScs. The migration ability of BM-MScs was evaluated following transfection of the cells with the mimics or antagonists of miRNA (miR)-27b, miR-146a, miR‐155 and miR‐154. miR‐155 significantly inhibited cell migration. Myosin light chain kinase (MYLK) was identified as the direct target of miR-155 in BM-MScs, which was further investigated using the luciferase reporter assay. However, miR-155 did not affect the expression of upstream proteins of the RhoA pathway controlling the activity of MYLK, suggesting that miR-155 directly suppressed the expression of MYLK without affecting the RhoA pathway. These results may facilitate the development and clinical use of BM-MScs in terms of their migration. Introduction MicroRNAs (miRNAs) are a class of small, non-coding RNAs (length, ~22 nt), which regulate gene expression at the post-transcriptional level. miRNAs are involved in the regulation of the majority of important biological events, including differentiation, growth, proliferation, survival, signal transduction and immune response (1-3). However, the roles of miRNAs in the activation of human bone marrow-derived mesenchymal stromal cells (BM-MScs) remain to be elucidated. BM-MScs are multipotent cells that differentiate into osteoblasts, adipocytes, chondrocytes and other tissue cells (4-7). MScs not only support hematopoiesis and regulate immunity, but also specifically migrate to sites of tissue damage, chronic inflammation and tumors (8‐11). For tumor therapy, MScs can be used as a carrier for tumor resistance proteins, including interferon-α and -β, and specifically migrate to tumor sites to inhibit tumor cell growth (12,13). MScs can also home to bone marrow, repair damage in the hematopoietic microenvironment and promote hematopoietic reconstruction in patients following hematopoietic stem cell transplantation (14). MScs have broad application prospects, however, the mechanism of MSc migration remains to be fully elucidated. An in-depth understanding of the mechanisms of MSc migration may enhance treatment efficiency by improving the ability of MSCs to migrate to target organs. Toll-like receptors (TLRs) are an important class of protein molecules involved in innate immunity and acquired immunity (15). It has been demonstrated that TLRs are expressed in MScs to modulate their proliferation, cytokine secretion, differentiation, hematopoiesis-supporting functions and immunosuppressive capacity (16,17). Previous studies have suggested that the activation of TLR2 inhibits the migration of mice BM-MScs (18). In our previous study, it was demonstrated that TLR2 was expressed on the surface of BM-MScs and can suppress their migration (19). Notably, it is well established that TLRs induce multiple miRNAs, which in turn fine‐tunes TLR‐signaling responses at multiple levels. For example, miRNA (miR)-105, miR-146 and the let-7 miRNA family directly target the expression of TLR2 and TLR4 (20-23), whereas miR-155 and miR-146b target numerous TLR downstream signaling proteins (24,25). Regulatory molecules, TLR-induced transcription factors and MicroRNA‐155 targets myosin light chain kinase to inhibit the migration of human bone marrow‐derived mesenchymal stem cells XINGBING WANG1, XU YE1, JINGJUAN JI2, JIAN WANG1, BO XU2, QIAN ZHANG1, JING MING1 and XIN LIU1 1department of Hematology and 2Reproductive Medicine Center, The First Affiliated Hospital, University of Science and Technology of china, Hefei, Anhui 230001, P.R. china Received July 8, 2017; Accepted May 31, 2018 dOI: 10.3892/ijmm.2018. 3718 Correspondence to: dr Xingbing Wang, department of Hematology, The First Affiliated Hospital, University of Science and Technology of china, 17 Lujiang Road, Hefei, Anhui 230001,