lncRNA GAS5 promotes M1 macrophage polarization via miR‐455‐5p/SOCS3 pathway in childhood pneumonia

Abstract

Objectives We herein aimed to explore whether growth arrest‐specific 5 (GAS5) promotes M1 macrophage polarization in childhood pneumonia and to investigate the underlying mechanism. Methods Relative GAS5 and miR‐455‐5p expression and suppressor of cytokine signaling 3 (SOCS3) messenger RNA level were examined using quantitative reverse transcription polymerase chain reaction. Protein expression of SOCS3 and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway‐related proteins was detected using western blot analysis. Luciferase activity assay was performed to test whether miR‐455‐5p could bind to GAS5 or SOCS3. The macrophage phenotype was determined using flow cytometry analysis and enzyme‐linked immunosorbent assay. Results The macrophage polarization toward the M2 phenotype was observed in peripheral blood from pneumonia children. Furthermore, GAS5 and SOCS3 expression were upregulated but miR‐455‐5p downregulated in human monocyte‐derived macrophages from pneumonia children compared with the control group. Furthermore, GAS5 acted as a sponge for miR‐455‐5p to facilitate SOCS3 expression. Moreover, miR‐455‐5p mimic and SOCS3 knockdown significantly reversed the GAS5 overexpression‐mediated suppression of the JAK2/STAT3 signaling and promotion of M1 polarization. Conclusion GAS5 promotes M1 macrophage polarization by acting as a competing endogenous RNA of miR‐455‐5p to facilitate SOCS3 expression in childhood pneumonia.

Long noncoding RNA GAS5 does not regulate HBV replication

“…GAS5, previously known as growth arrest‐specific transcript 5, is widely considered as a tumor suppressor. Emerging evidence already illustrated the close relationship between dysregulated GAS5 and an extensive array of human diseases, including cancers from breast cancer to myeloma, autoimmune disorders, liver fibrosis, and childhood pneumonia . GAS5 played significant roles in diverse cellular processes through mediating cell cycle, apoptosis, autophagy, drug resistance, or inflammatory response .…”

Long non‐coding RNA expressed in macrophage co‐varies with the inflammatory phenotype during macrophage development and polarization

“…Knockdown of lncRNA‐MM2P in RAW264.7 could cut down the M2 polarization by decreasing phosphorylation level of STAT6 . LncRNA growth‐arrest‐specific transcript 5 (GAS5) was up‐regulated in human monocyte‐derived macrophages from pneumonia children and acted as a miR‐455‐5p decoy to up‐regulate SOCS3, then inhibited JAK2/STAT3 signalling and increased the transformation of M1 macrophage (Figure and Table ).…”

Non-coding RNAs in pneumonia diagnosis

“…Трансфекция макрофагов, полученных из моноцитов периферической крови, вектором, обеспечивавшим сверхэкспрессию GAS5, приводила к их поляризации в фенотип М1, усилению в них экспрессии SOCS3 и подавлению сигнального пути JAK2/STAT3. На основании полученных данных авторы выдвинули гипотезу, что GAS5 является «ловушкой» для miR-455-5p, облегчая в итоге супрессию сигнального пути JAK2/STAT3, участвующего в том числе в индукции поляризации макрофагов [53].…”