Molecular Mechanisms of microRNA-494 Involving in Cerebral Ischemia

NCT ID: NCT03577093

Last Updated: 2018-07-05

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-06-06
• Study Completion Date: 2021-12-31

Brief Summary

We and other investigations suggested that the activation of nerve cell cycle following cerebral ischemia led to neuronal apoptosis, glial cell proliferation and the formation of glial scar.The cyclin-dependent kinases (CDKs) and cyclins jointly promoted the cell cycle progression. Our preliminary clinical trial found a new microRNA-miR-494, which involved in the occurrence of acute ischemic stroke. In our animal experiment, miR-494 could relieve cerebral ischemia injury through inhibiting cyclin-dependent kinase 6(CDK6), ubiquitin-conjugating enzyme E2L6 (UBE2L6) and histone deacetylase 3 (HDAC3), which suggested that miR-494 might play an important role in the regulation of cell cycle following cerebral ischemia. This project intends to verify the following hypothesis：①miR-494 suppresses CDK6, and/or fibroblast growth factor16(FGF16)-Ras-extracellular signal-regulated kinase(ERK)--v-myc avian myelocytomatosis viral oncogene homolog(MYC) pathway, and/or phosphatase and tensin homolog(PTEN)-/protein kinase B(AKT)-mechanistic target of rapamycin(mTOR)-S6k pathway;②miR-494 inhibits UBE2L6, upregulates the hypoxia-inducible factor 1 α(HIF-1α) expression in nerve cells, thereby increases the p21 and p27 protein levels and inhibits cyclin-dependent kinase2(CDK2)activity;③miR-494 represses HDAC3 and downregulates the cyclin-dependent kinase1(CDK1)protein level. These all mediate the cell cycle arrest of neurons and astrocytes, reduce the neuronal apoptosis and glial scar formation,promote the recovery of neurological function and provide new targets for the treatment of ischemic stroke.

Conditions

Ischemic Stroke

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

ischemic stroke

acute ischemic stroke patients within 6h after stroke onset

There is no intervention at all.

Intervention Type: OTHER

There is no intervention at all.

control

healthy controls

There is no intervention at all.

Intervention Type: OTHER

There is no intervention at all.

Interventions

There is no intervention at all.

There is no intervention at all.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• (1）diagnosis of first ischemic stroke based on clinical information and magnetic resonance imaging; (2)presentation of subjects within 6h of the event; (3)National Institutes of Health Stroke Scale (NIHSS) score between 4 and 15.

Exclusion Criteria

• (1）suspected cardiogenic embolism;(2）secondary stroke from cerebral hemorrhage, trauma, cancer or aneurysm and so on;(3）bleeding tendency;(4）severe cardiac,pulmonary,hepatic or renal insufficiency;(5）Vital signs are unstable to be assessed.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Capital Medical University

OTHER

Sponsor Role: lead

Responsible Party

Ji Xunming,MD,PhD

Vice President of Xuanwu Hospital,Capital Medical University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luo Yumin

Role: PRINCIPAL_INVESTIGATOR

Capital Medical University

Locations

Xuanwu Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Luo Yumin

Role: CONTACT

yumin111@ccmu.edu.cn

01083198129

Facility Contacts

Luo Yumin

Role: primary

yumin111@ccmu.edu.cn

01083198129

References

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Reference Type: BACKGROUND

PMID: 24302516 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 23613494 (View on PubMed)

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PMID: 24828495 (View on PubMed)

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Fournier M, Orpinell M, Grauffel C, Scheer E, Garnier JM, Ye T, Chavant V, Joint M, Esashi F, Dejaegere A, Gonczy P, Tora L. KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification. Nat Commun. 2016 Oct 31;7:13227. doi: 10.1038/ncomms13227.

Reference Type: RESULT

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Jiang Y, Hsieh J. HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels. Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13541-6. doi: 10.1073/pnas.1411939111. Epub 2014 Aug 26.

Reference Type: RESULT

PMID: 25161285 (View on PubMed)

Li G, Ma X, Zhao H, Fan J, Liu T, Luo Y, Guo Y. Long non-coding RNA H19 promotes leukocyte inflammation in ischemic stroke by targeting the miR-29b/C1QTNF6 axis. CNS Neurosci Ther. 2022 Jun;28(6):953-963. doi: 10.1111/cns.13829. Epub 2022 Mar 24.

Reference Type: DERIVED

PMID: 35322553 (View on PubMed)

Other Identifiers

miR-494

Identifier Type: -

Identifier Source: org_study_id