LncRNA SNHG1 alleviated apoptosis and inflammation during ischemic stroke by targeting miR-376a and modulating CBS/H₂S pathway

Abstract

Background

Ischemic stroke (IS) is a major public health issue causing mortality and disability and is more difficult to treat than other cerebral diseases. Previous study reported that miR-376a was upregulated in the serum of stroke patients, indicating that miR-376a played potential role in occurrence and development of stroke.

Methods

IS cell model was induced by oxygen-glucose deprivation (OGD) exposed HCMEC/D3 cells. The mRNA level of SNHG1, miR-376a and inflammatory cytokines were detected by q-PCR. Protein level of CBS, apoptotic proteins were examined by Western blot. Apoptosis was analyzed by flow cytometry, and H₂S level was measured by kit. Interaction among lncRNA, miRNA and target gene was validated by luciferase assay.

Results

Our research revealed that mRNA level of SNHG1 and CBS in HCMEC/D3 cells was downregulated while miR-376a was upregulated under OGD conditions. Further results demonstrated that miR-376a overexpression promoted apoptosis and inflammation while SNHG1 overexpressing alleviated such processes. Mechanistically, SNHG1 directly targeted miR-376a, and CBS was a target of miR-376a. Moreover, SNHG1 exert its function via inhibiting miR‐376a to regulate CBS expression.

Conclusion

LncRNA SNHG1 depressed apoptosis and inflammation of IS cell model via inhibiting miR-376a and upregulating CBS/H₂S signal. These results show light on underlying mechanisms of IS and provide potential targets for IS therapy.

Keywords:

• ischemic stroke
• SNHG1
• miR-376a
• CBS
• H2S

Disclosure statement

The authors declare that they have no conflict of interests.

Funding

None.

Availability of data and material

All data generated or analyzed during this study are included in this published article

Authors’ contributions

Guarantor of integrity of the entire study: Xiang-Yang Zhou; study concepts: Li Lv; study design: Li Lv, Xiang-Yang Zhou; definition of intellectual content: Li Lv, Xiang-Yang Zhou; literature research: Hai-Peng Xi; experimental studies: Li Lv, Hai-Peng Xi, Jian-Chao Huang; data acquisition: Hai-Peng Xi; data analysis: Li Lv, Hai-Peng Xi; statistical analysis: Jian-Chao Huang, Xiang-Yang Zhou; manuscript preparation: Li Lv, Xiang-Yang Zhou; manuscript editing: Xiang-Yang Zhou; manuscript review: Xiang-Yang Zhou.