Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142 -TIPARP: implications for cerebral ischemic stroke
Open accessAbstract
Circular RNAs (circRNAs) are highly expressed in the central nervous system and are involved in the regulation of physiological and pathophysiological processes. However, the potential role of circRNAs in stroke remains largely unknown. Here, using a circRNA microarray, we showed that circular RNA Hectd1 (circHectd1) levels were significantly increased in ischemic brain tissues in transient middle cerebral artery occlusion (tMCAO) mouse stroke models and further validated this finding in plasma samples from acute ischemic stroke (AIS) patients. Knockdown of circHectd1 expression significantly decreased infarct areas, attenuated neuronal deficits, and ameliorated astrocyte activation in tMCAO mice. Mechanistically, circHECTD1 functions as an endogenous MIR142 (microRNA 142) sponge to inhibit MIR142 activity, resulting in the inhibition of TIPARP (TCDD inducible poly[ADP-ribose] polymerase) expression with subsequent inhibition of astrocyte activation via macroautophagy/autophagy. Taken together, the results of our study indicate that circHECTD1 and its coupling mechanism are involved in cerebral ischemia, thus providing translational evidence that circHECTD1 can serve as a novel biomarker of and therapeutic target for stroke. ABBREVIATIONS: 3-MA: 3-methyladenine; ACTB: actin beta; AIS: acute ischemic stroke; AS: primary mouse astrocytes; BECN1: beclin 1, autophagy related; BMI: body mass index; circHECTD1: circRNA HECTD1; circRNAs: circular RNAs; CBF: cerebral blood flow; Con: control; DAPI: 4',6-diamidino-2-phenylindole; ECA: external carotid artery; FISH: fluorescence in situ hybridization; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; Gdna: genomic DNA; GFAP: glial fibrillary acidic protein; GO: gene ontology; HDL: high-density lipoprotein; IOD: integrated optical density; LDL: low-density lipoprotein; LPA: lipoprotein(a); MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MIR142: microRNA 142; mNSS: modified neurological severity scores; MRI: magnetic resonance imaging; NIHSS: National Institute of Health Stoke Scale; OGD-R: oxygen glucose deprivation-reperfusion; PCR: polymerase chain reaction; PFA: paraformaldehyde; SQSTM1: sequestosome 1; TIPARP: TCDD inducible poly(ADP-ribose) polymerase; tMCAO: transient middle cerebral artery occlusion; TTC: 2,3,5-triphenyltetrazolium chloride; UTR: untranslated region; WT: wild type.
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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 [109]
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- Authors
- Han, B., Zhang, Y., Zhang, Y., Bai, Y., Chen, X., Huang, R., Wu, F., Leng, S., Chao, J., Zhang, J. H., Hu, G., & Yao, H.
- Affiliations
- Southeast University (CN)
- Jiangsu Province Hospital (CN)
- Loma Linda University (US)
- Nanjing Medical University (CN)
- Corresponding author
- Yao, Honghong
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2018-07-03
- Volume
- 14
- Issue
- 7
- Pages
- 1164-1184
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC6103660
- OpenAlex
- W2810401400
- Cited by
- 360
- References
- 74
- Citations by year
- 2026: 13 · 2025: 35 · 2024: 38 · 2023: 59 · 2022: 60 · 2021: 64 · 2020: 53 · 2019: 33 · 2018: 5
- FWCI
- 13.96
- 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 (81673410, 81473190, 81603090)
- Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYZZ16_0127)
- Major State Basic Research Developmen (2013CB733800/2013CB733803)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- circular RNA, acute ischemic stroke, astrocyte activation, TIPARP, microRNA sponge, transient middle cerebral artery occlusion, stroke biomarkers, therapeutic target, infarct size, neuroinflammation, plasma biomarkers, circRNA microarray
- MeSH terms
- RNA, Circular, Aged, Animals, Astrocytes, Autophagy, Base Sequence, Brain Ischemia, Female, Humans, Male, Mice, Inbred C57BL, Poly(ADP-ribose) Polymerases, RNA, Up-Regulation, Infarction, Middle Cerebral Artery, Brain Infarction, Stroke, Nucleoside Transport Proteins, MicroRNAs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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