PMID- 30742923 OWN - NLM STAT- MEDLINE DCOM- 20190712 LR - 20191210 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) VI - 129 DP - 2019 May 15 TI - Circular RNA circPTK2 regulates oxygen-glucose deprivation-activated microglia-induced hippocampal neuronal apoptosis via miR-29b-SOCS-1-JAK2/STAT3-IL-1beta signaling. PG - 488-496 LID - S0141-8130(18)36945-9 [pii] LID - 10.1016/j.ijbiomac.2019.02.041 [doi] AB - Oxygen-glucose deprivation (OGD)-activated microglia contribute to neuronal apoptosis via releasing pro-inflammatory cytokines, and some miRNAs have been reported to be involved in this process. Circular RNAs (circRNAs) have been reported to function as miRNA sponges, but it remains unknown whether and how circRNAs contribute to OGD-activated microglia-induced neuronal apoptosis. Here, we investigated the function and relationship of miR-29b and circPTK2 in OGD-activated microglia-induced neuronal apoptosis. We found upregulation of TNF-alpha and IL-1beta, and downregulation of miR-29b in OGD-activated microglia. miR-29b inhibited OGD-activated microglia-induced neuronal apoptosis. Meanwhile, miR-29b promoted SOCS-1 expression, and suppressed JAK2/STAT3 signaling. In addition, inhibition of JAK2/STAT3 signaling downregulated IL-1beta expression, while upregulation of miR-29b or SOCS-1 also inhibited IL-1beta production. IL-1beta was confirmed to be an apoptosis inducer of hippocampal neurons. Moreover, either SOCS-1 upregulation or blockade of JAK2/STAT3 signaling suppressed OGD-activated microglia-induced neuronal apoptosis. These data suggest that miR-29b inhibits OGD-activated microglia-induced neuronal apoptosis via inducing SOCS-1 expression, blocking JNK2/STAT3 signaling, and inhibiting IL-1beta production. circPTK2 was confirmed to inhibit miR-29b expression in OGD model by directly binding to miR-29b. Function assay showed that circPTK2 regulated microglia-induced neuronal apoptosis via sponging miR-29b. Collectively, these findings suggest that circPTK2 regulates OGD-activated microglia-induced neuronal apoptosis via miR-29b-SOCS-1-JAK2/STAT3-IL-1beta signaling. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Wang, Huilin AU - Wang H AD - Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Li, Zheng AU - Li Z AD - Clinical Science Institute of Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Gao, Jingyan AU - Gao J AD - Department of Human Anatomy and Histo-Embryology, Shanghai Medical College of Fudan University, Shanghai, China. FAU - Liao, Qingwu AU - Liao Q AD - Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: liao.qingwu@zs-hospital.sh.cn. LA - eng PT - Journal Article DEP - 20190208 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 RN - 0 (Interleukin-1beta) RN - 0 (MIRN29 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (STAT3 Transcription Factor) RN - 0 (Socs1 protein, rat) RN - 0 (Suppressor of Cytokine Signaling 1 Protein) RN - 63231-63-0 (RNA) RN - EC 2.7.10.2 (Focal Adhesion Kinase 1) RN - EC 2.7.10.2 (Janus Kinase 2) RN - EC 2.7.10.2 (Ptk2 protein, rat) RN - IY9XDZ35W2 (Glucose) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Apoptosis/*genetics MH - Cell Hypoxia/genetics MH - Female MH - Focal Adhesion Kinase 1/genetics MH - Glucose/*metabolism MH - Hippocampus/cytology MH - Interleukin-1beta/metabolism MH - Janus Kinase 2/metabolism MH - MicroRNAs/*genetics MH - Microglia/*cytology MH - Neurons/*cytology MH - Oxygen/*metabolism MH - Pregnancy MH - RNA/*genetics MH - RNA, Circular MH - Rats MH - Rats, Sprague-Dawley MH - STAT3 Transcription Factor/metabolism MH - Signal Transduction/genetics MH - Suppressor of Cytokine Signaling 1 Protein/metabolism MH - Up-Regulation/genetics OTO - NOTNLM OT - Apoptosis OT - Hippocampal neuron OT - Microglia OT - Oxygen-glucose deprivation OT - circPTK2 OT - miR-29b EDAT- 2019/02/12 06:00 MHDA- 2019/07/13 06:00 CRDT- 2019/02/12 06:00 PHST- 2018/12/13 00:00 [received] PHST- 2019/02/07 00:00 [revised] PHST- 2019/02/07 00:00 [accepted] PHST- 2019/02/12 06:00 [pubmed] PHST- 2019/07/13 06:00 [medline] PHST- 2019/02/12 06:00 [entrez] AID - S0141-8130(18)36945-9 [pii] AID - 10.1016/j.ijbiomac.2019.02.041 [doi] PST - ppublish SO - Int J Biol Macromol. 2019 May 15;129:488-496. doi: 10.1016/j.ijbiomac.2019.02.041. Epub 2019 Feb 8.