Cerebral ischemic stroke (CIS) is a significant cause of disability and death. Inflammation usually occurs after CIS and accelerates cellular damage. NLRP3 plays a key role in the formation of CIS‑associated inflammasome. Understanding how NLRP3 is regulated bears great importance. We hypothesized that lncRNA NEAT1 can downregulate NLRP3 expression by regulating the miR‑10b‑5p/BCL6 axis, and thus regulate microglia‑driven inflammation. The expression of NEAT1 was analyzed in CIS patients and an in vitro model of oxygen and glucose deprivation/re‑oxygenation (OGD/R). We assessed the levels of pro‑inflammatory cytokines IL‑18 and IL‑1β with ELISA. Interactions between NEAT1/miR‑10b‑5p and miR‑10b‑5p/BCL6 were determined by luciferase assay. The interaction of BCL6 and NLRP3 was identified by ChIP; RNA, and protein levels were evaluated by qRT‑PCR and western blot, respectively. We found that NEAT1 level was decreased in CIS patients and OGD/R treated cells. OGD/R exerted pro‑inflammasome effects by increasing the expression of inflammasome‑associated proteins and ROS and malondialdehyde (MDA) while inhibiting SOD production. This effect was partially antagonized by NEAT1. We bioinformatically identified interactions between NEAT1/miR‑10b‑5p, BCL6/miR‑10b‑5p, and NLRP3‑promoter/BCL6, and validated them by luciferase assay, qRT‑PCR, and ChIP. NEAT1 inhibited miR‑10b‑5p and upregulated BCL6 by ceRNA mechanism and alleviated OGD/R induced cell damage. We also proved that BCL6 was a repressive transcription factor in the regulation of NLRP3 expression. Thus, lncRNA NEAT1 inhibited inflammasome activation by NLRP3 in microglia via the NEAT1/ miR‑10b‑5p/BCL6/NLRP3 regulatory axis, which alleviated deleterious outcomes of ischemic stroke.
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http://dx.doi.org/10.55782/ane-2022-002 | DOI Listing |
J Transl Med
January 2025
Emergency Department, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
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Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Objectives: Parkinson's disease (PD) is a complex neurodegenerative disease with unclear pathogenesis. Some recent studies have shown that there is a close relationship between PD and ferroptosis. We aimed to identify the ferroptosis-related genes (FRGs) and construct competing endogenous RNA (ceRNA) networks to further assess the pathogenesis of PD.
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December 2024
Faculty of Medicine, Department of Medical Biochemistry and Molecular Biology, Fayoum University, Fayoum, Egypt.
Background: The SARS-CoV-2 virus's frequent mutations have made disease control with vaccines and antiviral drugs difficult; as a result, there is a need for more effective coronavirus drugs. Therefore, detecting the expression of various diagnostic biomarkers, including ncRNA in SARS-CoV2, implies new therapeutic strategies for the disease.
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Cancer Lett
December 2024
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:
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December 2024
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address:
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