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      MiR-155 promotes compensatory lung growth by inhibiting JARID2 activation of CD34 + endothelial progenitor cells

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          Abstract

          Bone marrow-derived CD34-positive (CD34 +) endothelial progenitor cells (EPCs) has unique functions in the mechanism of compensatory lung growth (CLG). The content of this study is mainly to describe the effect of microRNA (miR)-155 in the mechanisms of EPCs and CLG. Our study found that transfection of miR-155 mimic could promote EPC proliferation, migration and tube formation, while transfection of miR-155 inhibitor had the opposite effect. It was also found that transfection of pc-JARID2 inhibited EPC proliferation, migration and tube formation, while transfection of si-JARID2 had the opposite effect. miR-155 can target and negatively regulate JARID2 expression. Overexpression of JARID2 weakened the promoting effects of miR-155 mimic on EPC proliferation, migration, and tubular formation, while silencing JARID2 weakened the inhibitory effects of miR-155 inhibitors on EPC proliferation, migration, and tubular formation. Transplantation of EPCs transfected with miR-155 mimic into the left lung model effectively increased lung volume, total alveolar number, diaphragm surface area, and lung endothelial cell number, while transplantation of EPCs co-transfected with miR-155 mimic and pc-JARID2 reversed this phenomenon. Overall, we found that miR-155 activates CD34 + EPC by targeting negative regulation of JARID2 and promotes CLG.

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          Most cited references45

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          Deciphering miRNAs’ Action through miRNA Editing

          MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called “RNA editing” involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA’s stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA’s ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.
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            Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer

            MicroRNA-155 (miR-155) is frequently up-regulated in various types of human cancer; however, its role in cancer angiogenesis remains unknown. Here, we demonstrate the role of miR-155 in angiogenesis through targeting von Hippel-Lindau tumour suppressor (VHL) in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited HUVEC network formation, proliferation, invasion, and migration. Furthermore, mammary fat pad xenotransplantation of ectopically expressed miR-155 resulted in extensive angiogenesis, proliferation, tumour necrosis, and recruitment of pro-inflammatory cells such as tumour associated macrophages. Expression of VHL abrogated these miR-155 effects. Moreover, miR-155 expression inversely correlates with VHL expression level and is associated with late stage, lymph node metastasis, and poor prognosis as well as triple-negative tumour in breast cancer. These findings indicate that miR-155 plays a pivotal role in tumour angiogenesis by downregulation of VHL, and provide a basis for miR-155-expressing tumours to embody an aggressive malignant phenotype, and therefore, miR-155 is an important therapeutic target in breast cancer.
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              Requirement of bic/microRNA-155 for normal immune function.

              MicroRNAs are a class of small RNAs that are increasingly being recognized as important regulators of gene expression. Although hundreds of microRNAs are present in the mammalian genome, genetic studies addressing their physiological roles are at an early stage. We have shown that mice deficient for bic/microRNA-155 are immunodeficient and display increased lung airway remodeling. We demonstrate a requirement of bic/microRNA-155 for the function of B and T lymphocytes and dendritic cells. Transcriptome analysis of bic/microRNA-155-deficient CD4+ T cells identified a wide spectrum of microRNA-155-regulated genes, including cytokines, chemokines, and transcription factors. Our work suggests that bic/microRNA-155 plays a key role in the homeostasis and function of the immune system.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: InvestigationRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Software
                Role: Data curationRole: Software
                Role: Formal analysis
                Role: Methodology
                Role: Methodology
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                23 February 2024
                2024
                : 19
                : 2
                : e0296671
                Affiliations
                [1 ] Department of Anesthesiology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, Yunnan, China
                [2 ] Department of Palliative Medicine, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, Yunnan, China
                [3 ] Department of Gynaecologic Oncology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, Yunnan, China
                [4 ] Department of Anesthesiology, The 6th Affiliated Hospital of Kunming Medical University (The People’s Hospital of Yuxi City), Yuxi, 653100, Yunnan, China
                [5 ] Department of Thoracic Surgery Ⅱ, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, Yunnan, China
                Xiangya Hospital Central South University, CHINA
                Author notes

                Competing Interests: The authors declare that they have no competing interests.

                Author information
                https://orcid.org/0000-0002-3268-8001
                Article
                PONE-D-23-15191
                10.1371/journal.pone.0296671
                10890733
                38394221
                871869b3-e935-4be7-b014-4d91a31b917e
                © 2024 Zhao et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 June 2023
                : 13 December 2023
                Page count
                Figures: 8, Tables: 0, Pages: 17
                Funding
                Funded by: Yunnan Provincial Science and Technology Department-Kunming Medical University
                Award ID: 202201AY070001-137
                Funded by: Joint Special Fund for Applied Basic Research of Yunnan Provincial Science and Technology Department-Kunming Medical University
                Award ID: 202101AY070001-170
                Award Recipient :
                Funded by: Joint Special Fund for Applied Basic Research of Yunnan Provincial Science and Technology Department-Kunming Medical University
                Award ID: 202301AY070001-085
                This study was supported by Yunnan Provincial Science and Technology Department-Kunming Medical University (Grant No.202201AY070001-137); Joint Special Fund for Applied Basic Research of Yunnan Provincial Science and Technology Department-Kunming Medical University (No. 202101AY070001-170, No. 202301AY070001-085).
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