1. Downregulation of microRNA-144 inhibits proliferation and promotes the apoptosis of myelodysplastic syndrome cells through the activation of the AKAP12-dependent ERK1/2 signaling pathway.
- Author
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Qian W, Jin F, Zhao Y, Chen Y, Ge L, Liu L, and Yang M
- Subjects
- A Kinase Anchor Proteins genetics, Animals, Base Sequence, Cell Cycle Checkpoints genetics, Cell Cycle Proteins genetics, Cell Proliferation genetics, Female, Gene Expression Profiling, Mice, Nude, Mice, SCID, MicroRNAs genetics, Models, Biological, Protein Binding, RNA, Messenger genetics, RNA, Messenger metabolism, Up-Regulation genetics, A Kinase Anchor Proteins metabolism, Apoptosis genetics, Cell Cycle Proteins metabolism, Down-Regulation genetics, MAP Kinase Signaling System, MicroRNAs metabolism, Myelodysplastic Syndromes genetics
- Abstract
Background: Myelodysplastic syndromes (MDS) represent a family of hematopoietic stem cell disorders characterized by ineffective hematopoiesis. While the functions of many microRNAs have been identified in MDS, microRNA-144 (miR-144) remains poorly understood. Thus, the aim of the present study was to determine the effects of miR-144 on cell proliferation and apoptosis in MDS cells and mechanism thereof., Methods: MDS-related microarrays were used for screening differentially expressed genes in MDS. The relationship between miR-144 and A-kinase anchoring protein 12 (AKAP12) was determined by a dual luciferase reporter gene assay. Subsequently, gain- and loss-function approaches were used to assess the effects of miR-144 and AKAP12 on cell proliferation, cell cycle and cell apoptosis by MTT assay and flow cytometry. Following the induction of a mouse model with MDS, the tumor tissues were extract for evaluation of apoptosis and the expression of miR-144, AKAP12, and the relevant genes associated with extracellular-regulated protein kinases 1/2 (ERK1/2) signaling pathway and apoptosis., Results: We observed significantly diminished expression of AKAP12 in MDS samples. miR-144 directly bound to AKAP12 3'UTR and reduced its expression in hematopoietic cells. Downregulation of miR-144 or upregulation of AKAP12 was observed to prolong cell cycle, inhibit cell proliferation, and induce apoptosis, accompanied by increased expression of AKAP12, p-ERK1/2, caspase-3, caspase-9, Bax, and p53, as well as decreased expression of Bcl-2. The transplanted tumors in mice with down-regulated miR-144 exhibited a lower mean tumor diameter and weight, and increased apoptosis index and expression of AKAP12 and ERK1/2., Conclusion: Taken together, these studies demonstrate the stimulative role of miR-144 in MDS progression by regulating AKAP12-dependent ERK1/2 signaling pathway., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
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