Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124–2HG
Open accessAbstract
Circular RNAs are a subclass of noncoding RNAs in mammalian cells; however, whether these RNAs are involved in the regulation of astrocyte activation is largely unknown. Here, we have shown that the circular RNA HIPK2 (circHIPK2) functions as an endogenous microRNA-124 (MIR124-2HG) sponge to sequester MIR124-2HG and inhibit its activity, resulting in increased sigma non-opioid intracellular receptor 1 (SIGMAR1/OPRS1) expression. Knockdown of circHIPK2 expression significantly inhibited astrocyte activation via the regulation of autophagy and endoplasmic reticulum (ER) stress through the targeting of MIR124-2HG and SIGMAR1. These findings were confirmed in vivo in mouse models, as microinjection of a circHIPK2 siRNA lentivirus into mouse hippocampi inhibited astrocyte activation induced by methamphetamine or lipopolysaccharide (LPS). These findings provide novel insights regarding the specific contribution of circHIPK2 to astrocyte activation in the context of drug abuse as well as for the treatment of a broad range of neuroinflammatory disorders.
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CircHECTD1 and circHIPK2 activate astrocytes via autophagic processes that target miR142-TIPARP and miR124-2HG, respectively.
“Circular HECTD1 (CircHECTD1) and circHIPK2 activate astrocytes via autophagic processes that target miR142-TIPARP and miR124-2HG, respectively [108,109].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [108]
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- Authors
- Huang, R., Zhang, Y., Han, B., Bai, Y., Zhou, R., Gan, G., Chao, J., Hu, G., & Yao, H.
- Affiliations
- Southeast University (CN)
- University of Science and Technology of China (CN)
- Nanjing Medical University (CN)
- Corresponding author
- Yao, Honghong
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2017-09-07
- Volume
- 13
- Issue
- 10
- Pages
- 1722-1741
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC5640207
- OpenAlex
- W2743353724
- Cited by
- 278
- References
- 56
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 27 · 2023: 30 · 2022: 36 · 2021: 69 · 2020: 32 · 2019: 34 · 2018: 24 · 2017: 2
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (2013CB733800, 2013CB733803, 81603090, 81673410, 81322048)
- Major State Basic Research Development Program of China (2013CB733800, 2013CB733803)
- National Key Research and Development Program of China (2013CB733800, 2013CB733803)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- circular RNA, astrocyte activation, microRNA sponge, sigma-1 receptor, endoplasmic reticulum stress, methamphetamine, lipopolysaccharide, neuroinflammation, drug abuse, hippocampus
- MeSH terms
- RNA, Circular, Animals, Animals, Newborn, Astrocytes, Autophagy, Carrier Proteins, Cells, Cultured, Encephalitis, Gene Expression Regulation, Humans, Male, Mice, Inbred C57BL, RNA, Protein Serine-Threonine Kinases, Mice, Knockout, MicroRNAs, Mice, HEK293 Cells, Endoplasmic Reticulum Stress
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