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Published on: February 21, 2018
MiR-886-3p down regulates CXCL12 (SDF1) expression in human marrow stromal cells
Manoj M Pillai1, Xiaodong Yang, Ilango Balakrishnan
1Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America. Manoj.Pillai@UCDenver.edu
Insights
MicroRNA-886-3p significantly down-regulates Stromal Derived Factor 1 (SDF1 or CXCL12) expression in stromal cells. This suggests microRNAs play a role in regulating CXCL12, crucial for hematopoietic stem cell homing.
Area of Science:
- Molecular Biology
- Cell Biology
- Hematology
Background:
- Stromal Derived Factor 1 (SDF1 or CXCL12) is a key chemokine regulating cell migration, including hematopoietic stem cell (HSC) homing.
- Stromal cell lines exhibit functional differences and varying CXCL12 expression levels (CXCL12+ vs. CXCL12-).
Purpose of the Study:
- To investigate the role of microRNAs in regulating CXCL12 expression in stromal cells.
- To identify specific microRNAs involved in modulating CXCL12 levels and function.
Main Methods:
- Comparative analysis of miRNA expression profiles in CXCL12+ and CXCL12- stromal cell lines.
- Transfection of miR-886-3p into stromal cells to assess its effect on CXCL12 expression and function.
- Identification of the target site of miR-886-3p within the CXCL12 mRNA 3' untranslated region (UTR).
Main Results:
- CXCL12- stromal cells showed significantly higher expression (>40 fold) of miR-886-3p compared to CXCL12+ cells.
- Transfection of miR-886-3p into CXCL12+ stromal cells led to an 85% down-regulation of CXCL12 expression.
- miR-886-3p transfection resulted in the loss of CXCL12-directed chemotaxis and reduced CXCL12 expression in primary stromal cultures.
- miR-886-3p was confirmed to specifically target the 3' UTR of CXCL12 mRNA.
Conclusions:
- MicroRNA-886-3p plays a significant role in down-regulating CXCL12 expression.
- These findings highlight a novel mechanism by which microRNAs modulate CXCL12, impacting hematopoietic regulation.
- This study identifies a potential regulatory pathway for controlling CXCL12-mediated cellular processes.
Abstract:
Stromal Derived Factor 1 (SDF1 or CXCL12), is a chemokine known to be critical for the migration of cells in several tissue systems including the homing of the hematopoietic stem cell (HSC) to its niche in the bone marrow. A comparative analysis of miRNA expression profiles of two stromal cell lines, distinguishable by function and by CXCL12 expression (CXCL12+ and CXCL12-), revealed that the CXCL12- cells expressed>40 fold more miR-886-3p than the CXCL12+ cells. Screening studies showed that when miR-886-3p was transfected into the CXCL12+ stromal cells, the expression of CXCL12 was down-regulated by as much as 85% when compared to appropriate controls, and results in the loss of CXCL12-directed chemotaxis. Similar reductions in CXCL12 were obtained with the transfection of miR-886-3p into primary stromal cell cultures. Additional studies showed that miR-886-3p specifically targeted the 3' untranslated region (UTR) of CXCL12 mRNA. These data suggest a role for miRNA in modulating the expression of CXCL12, a gene product with a critical role in hematopoietic regulation.
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