ABSTRACT
MicroRNAs are key regulators of many biological processes, including cell differentiation. These small RNAs exert their function assembled in the RNA-induced silencing complexes (RISCs), where members of Argonaute (Ago) family of proteins provide a unique platform for target recognition and gene silencing. Here, by using myeloid cell lines and primary blasts, we show that Ago2 has a key role in human monocytic cell fate determination and in LPS-induced inflammatory response of 1,25-dihydroxyvitamin D3 (D3)-treated myeloid cells. The silencing of Ago2 impairs the D3-dependent miR-17-5p/20a/106a, miR-125b and miR-155 downregulation, the accumulation of their translational targets AML1, VDR and C/EBPß and monocytic cell differentiation. Moreover, we show that Ago2 is recruited on miR-155 host gene promoter and on the upstream region of an overlapping antisense lncRNA, determining their epigenetic silencing, and miR-155 downregulation. These findings highlight Ago2 as a new factor in myeloid cell fate determination in acute myeloid leukemia cells.
Subject(s)
Argonaute Proteins/metabolism , Leukemia, Myeloid, Acute/metabolism , Argonaute Proteins/genetics , Blotting, Western , CCAAT-Enhancer-Binding Proteins/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , Calcitriol/pharmacology , Cell Differentiation/drug effects , Cell Differentiation/physiology , Cell Line, Tumor , Core Binding Factor Alpha 2 Subunit/genetics , Core Binding Factor Alpha 2 Subunit/metabolism , HL-60 Cells , Humans , Leukemia, Myeloid, Acute/genetics , MicroRNAs/genetics , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolismSubject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Dexamethasone/pharmacology , Drug Resistance, Neoplasm/genetics , Homeodomain Proteins/metabolism , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Receptor, Notch1/antagonists & inhibitors , Receptors, Glucocorticoid/metabolism , Anti-Inflammatory Agents/pharmacology , Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors , Basic Helix-Loop-Helix Transcription Factors/genetics , Blotting, Western , Chromatin Immunoprecipitation , Homeodomain Proteins/antagonists & inhibitors , Homeodomain Proteins/genetics , Humans , Mutation/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Receptor, Notch1/genetics , Receptor, Notch1/metabolism , Receptors, Glucocorticoid/genetics , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factor HES-1 , Tumor Cells, CulturedABSTRACT
Kidney transplantation is quite a routine complex procedure, not without risks and consequences to the donor, the recipient, and the health care professionals. Kidney-related medical malpractice suits are growing rapidly, and for clinicians and surgeons, the risk of being sued can be only reduced by practicing high-quality medicine and by appropriately communicating with donors and recipients. Actually relevant guidelines are available including safety and quality assurance standards for procurements, preservation, processing, and distribution for organs to maximize their quality and thereby the rate of success of transplants and to minimize the risk of such a procedure. We also find it essential that practice of living donor kidney transplant is in line with the general rules of the Convention for the Protection of Human Rights and its Additional Protocol. In this article, financial incentives and insurance aspects related with living donors kidney transplants are also illustrated.
