MicroRNAs as New Players in Endocrinology
Chun Peng*
Department of Biology, York University, Toronto, Canada
MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating various physiological processes through their effects on modulating gene expression. Increasing evidence suggest that miRNAs are important players in Endocrinology. First, miRNAs can be secreted from cells and transported to target cells to regulate activities in the target cells. Second, miRNAs regulate the expression of signaling molecules, their receptors, as well as downstream signaling networks. Finally, hormones have been reported to regulate the expression level of miRNAs.
The placenta is a critical organ that supports pregnancy. We have been investigating the role of growth factors, such as transforming growth factor-b (TGF-b) and Nodal, and their modulating miRNAs in regulating placental development. We have shown that TGF-b and Nodal regulate several aspects of placental development, such as proliferation, apoptosis, invasion, and differentiation. We have also identified several miRNAs that target Nodal, TGF-b, and/or their receptors, as well as their downstream signaling pathways. For example, miR-378a-5p targets Nodal and Smad2 to promote trophoblast proliferation and invasion and to inhibit the differentiation of syncytiotrophoblasts. In addition, miR-376c targets activin receptor-like kinase (ALK)-5 and -7, which are type I receptors for TGF-b and Nodal respectively, to promote trophoblast invasion and the outgrowth of placental explants. Interestingly, we demonstrated that in a pregnancy-related disorder, preeclampsia, these miRNAs are dysregulated. Taken together, our findings strongly support the role of miRNAs in fine tuning the activity of Nodal/TGF-b to ensure proper placental development.
Acknowledgements: Supported by Canadian Institutes of Health Research
Key Words: microRNAs, placenta development, trophoblast differentiation, TGF-b signaling, preeclampsia
Chun Peng*
Department of Biology, York University, Toronto, Canada
MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating various physiological processes through their effects on modulating gene expression. Increasing evidence suggest that miRNAs are important players in Endocrinology. First, miRNAs can be secreted from cells and transported to target cells to regulate activities in the target cells. Second, miRNAs regulate the expression of signaling molecules, their receptors, as well as downstream signaling networks. Finally, hormones have been reported to regulate the expression level of miRNAs.
The placenta is a critical organ that supports pregnancy. We have been investigating the role of growth factors, such as transforming growth factor-b (TGF-b) and Nodal, and their modulating miRNAs in regulating placental development. We have shown that TGF-b and Nodal regulate several aspects of placental development, such as proliferation, apoptosis, invasion, and differentiation. We have also identified several miRNAs that target Nodal, TGF-b, and/or their receptors, as well as their downstream signaling pathways. For example, miR-378a-5p targets Nodal and Smad2 to promote trophoblast proliferation and invasion and to inhibit the differentiation of syncytiotrophoblasts. In addition, miR-376c targets activin receptor-like kinase (ALK)-5 and -7, which are type I receptors for TGF-b and Nodal respectively, to promote trophoblast invasion and the outgrowth of placental explants. Interestingly, we demonstrated that in a pregnancy-related disorder, preeclampsia, these miRNAs are dysregulated. Taken together, our findings strongly support the role of miRNAs in fine tuning the activity of Nodal/TGF-b to ensure proper placental development.
Acknowledgements: Supported by Canadian Institutes of Health Research
Key Words: microRNAs, placenta development, trophoblast differentiation, TGF-b signaling, preeclampsia