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Long non-coding RNA MIAT impairs neurological function in ischemic stroke via up-regulating microRNA-874-3p-targeted
Shuai Zhang1, Yue Zhang2, Na Wang1
1Department of Neurology, the Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China.
Objective:
Long non-coding RNAs (lncRNAs) have diagnostic and therapeutic values in the setting of ischemic stroke (IS). Here, we evaluated the value of myocardial infarction-associated transcript (MIAT) in IS with the involvement of microRNA (miR)-874-3p/interleukin (IL) 1B.
Methods:
MIAT, miR-874-3p and IL1B levels in serum of patients with IS were measured. A middle cerebral artery occlusion (MCAO) model was established in mice. MCAO mice were injected with Agomir of miR-874-3p, shRNA or overexpression vector of MIAT or siRNA of IL1B. Subsequently, behavioral activities and neurological function of mice were assessed. The number of Nissl bodies, brain damage, neuronal apoptosis and inflammatory factors in brain tissues of mice were measured. The targeting relationship between MIAT and miR-874-3p, as well as that between miR-874-3p and IL1B was explored.
Results:
In patients with IS, MIAT and IL1B were up-regulated and miR-874-3p was down-regulated. MIAT absorbed miR-874-3p while miR-874-3p targeted IL1B. Silencing of MIAT or IL1B, or promotion of miR-874-3p improved behavioral activities and neurological function of mice, reduced the number of Nissl bodies, as well as improved brain damage, neuronal apoptosis and inflammation. Overexpression of miR-874-3p abrogated up-regulated MIAT-mediated influence on MCAO mice.
Conclusion:
Shortly, this study figures out that MIAT impairs neurological function in IS via up-regulating miR-874-3p-targeted IL1B.
Insights
Myocardial infarction-associated transcript (MIAT) impairs neurological function in ischemic stroke by up-regulating microRNA-874-3p and interleukin-1B. Targeting MIAT or IL-1B, or promoting miR-874-3p, improves outcomes in stroke models.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) show promise for diagnosing and treating ischemic stroke (IS).
- The role of myocardial infarction-associated transcript (MIAT) in IS, particularly its interaction with microRNA-874-3p (miR-874-3p) and interleukin-1B (IL-1B), requires further investigation.
Purpose of the Study:
- To evaluate the diagnostic and therapeutic potential of MIAT in ischemic stroke.
- To elucidate the molecular mechanism involving MIAT, miR-874-3p, and IL-1B in IS.
Main Methods:
- Serum levels of MIAT, miR-874-3p, and IL-1B were measured in IS patients.
- A middle cerebral artery occlusion (MCAO) mouse model was used to assess the effects of manipulating MIAT, miR-874-3p, and IL-1B levels.
- Neurological function, brain damage, neuronal apoptosis, and inflammation were evaluated in MCAO mice.
Main Results:
- In IS patients, MIAT and IL-1B were upregulated, while miR-874-3p was downregulated.
- MIAT sponges miR-874-3p, and miR-874-3p targets IL-1B.
- Modulating MIAT, miR-874-3p, or IL-1B levels significantly impacted neurological function, brain damage, and inflammation in MCAO mice.
Conclusions:
- MIAT exacerbates neurological deficits in ischemic stroke by upregulating IL-1B through miR-874-3p inhibition.
- MIAT, miR-874-3p, and IL-1B represent potential therapeutic targets for ischemic stroke.
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