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Silencing of H19 alleviates oxygen–glucose deprivation/reoxygenation-triggered injury through the regulation of the miR-1306-5p/BCL2L13 axis

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Abstract

Cerebral ischemia/reperfusion (I/R) injury remains a leading cause of death and disability. Long noncoding RNAs (lncRNAs) exert key functions in cerebral I/R injury. Here, we sought to elucidate the mechanism underlying the regulation of H19 in cerebral I/R cell injury. An in vitro model of cerebral I/R injury was created using oxygen–glucose deprivation/reoxygenation (OGD/R). The levels of H19, miR-1306-5p and B cell lymphoma-2 (Bcl-2)-like 13 (BCL2L13) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability and apoptosis were determined by the Cell Counting-8 Kit (CCK-8) assay and flow cytometry, respectively. The levels of lactate dehydrogenase (LDH) and cytokines were evaluated by enzyme-linked immunosorbent assays (ELISA). Direct relationships among H19, miR-1306-5p and BCL2L13 were verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pulldown assays. Our data showed that H19 and BCL2L13 were highly expressed in the cerebral I/R injury rats and OGD/R-triggered SK-N-SH and IMR-32 cells. The knockdown of H19 or BLC2L13 alleviated OGD/R-triggered injury in SK-N-SH and IMR-32 cells. Moreover, H19 silencing protected against OGD/R-triggered cell injury by down-regulating BCL2L13. H19 acted as a sponge of miR-1306-5p and BCL2L13 was a direct target of miR-1306-5p. H19 mediated BCL2L13 expression by sequestering miR-1306-5p. Furthermore, miR-1306-5p was a molecular mediator of H19 function. These results suggested that H19 silencing alleviated OGD/R-triggered I/R injury at least partially depending on the regulation of the miR-1306-5p/BCL2L13 axis.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

The present study was supported by Science and Technology Development Fund of Hospital of Chengdu University of Traditional Chinese Medicine [2014-DYY-28]; National Administration of Traditional Chinese Medicine [IC20160225].

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Author notes

  1. Yuxing Huang, Lisha Deng and Lin Zeng contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39, Shierqiao Road, Chengdu, 610072, Sichuan, China

    Yuxing Huang, Lisha Deng, Lin Zeng, Kun Ye, Chengxun Li, Xiaolin Hou, Yuan Yao, Dingjun Li & Zhen Xiong

  2. Department of Neurosurgery, Quxian County People’s Hospital, No. 88, Heping Road, Dazhou, 635200, Sichuan, China

    Shanlin Bao

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  1. Yuxing Huang
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Contributions

All authors contributed to the study, conception, and design. Material preparation, data collection were performed by Yuxing Huang, Lisha Deng and Lin Zeng. Supervision was performed by Zhen Xiong and Dingjun Li. The first draft of the manuscript was written by Shanlin Bao and Kun Ye. Data analysis were performed by Chengxun Li, Xiaolin Hou and Yuan Yao. All authors read and approved the final manuscript.

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Correspondence to Zhen Xiong.

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Highlights

1. H19 acted as a sponge of miR-1306-5p and BCL2L13 was a direct target of miR-1306-5p.

2. H19 affected BCL2L13 expression by sequestering miR-1306-5p.

3. H19 silencing alleviated OGD/R-triggered I/R injury by regulating the miR-1306-5p/BCL2L13 axis.

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Huang, Y., Deng, L., Zeng, L. et al. Silencing of H19 alleviates oxygen–glucose deprivation/reoxygenation-triggered injury through the regulation of the miR-1306-5p/BCL2L13 axis. Metab Brain Dis 36, 2461–2472 (2021). https://doi.org/10.1007/s11011-021-00822-4

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  • DOI: https://doi.org/10.1007/s11011-021-00822-4

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