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Expression of Long Non-coding RNA RGD1566344 in the Brain Cortex of Male Mice After Focal Cerebral Ischemia–Reperfusion and the Neuroprotective Effect of a Non-coding RNA RGD1566344 Inhibitor

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Abstract

Ischemic stroke (IS) remains a major cause of disability and death. The changes in long non-coding RNA (lncRNA) RGD1566344 expression in the mouse cerebral cortex, including the infarct and penumbra regions after IS, are not clear. Less is known about the impact and underlying mechanisms of RGD1566344 in IS. In this study, we found that RGD1566344 levels were elevated in the ischemic infarct and penumbra regions 12 h after middle cerebral artery occlusion/reperfusion (MCAO/R) in male mice and in PC12 cells with oxygen glucose deprivation/reperfusion (OGD/R). The inhibition of RGD1566344 by small interference RNA (siRNA) significantly alleviated apoptosis in OGD/R PC12 cells. In cell transfection, quantitative real-time PCR, and Western blot experiments, we demonstrated the possible interaction of non-POU domain-containing octamer-binding protein (NONO) with RGD1566344. The NONO level in OGD/R PC12 cells was obviously increased after inhibiting the RGD1566344 treatment; subsequently the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was activated. This demonstrated the effect of the RGD1566344-NONO-AKT axis on neural protection after IS. These results revealed a new molecular mechanism of lncRNA RGD1566344 inhibitors through targeting NONO/AKT/mTOR signaling to protect against ischemic neuronal injury, providing strong evidence for the development of promising therapeutic strategies against IS.

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Acknowledgements

This study was supported by Special Financial Grant from the China Postdoctoral Science Foundation (2015T80592), General Financial Grant from the China Postdoctoral Foundation (2014M561720), and Key University Science Research Project of Jiangsu Province (16KJA310006). Postgraduate Research &Practice Innovation Program of Jiangsu Province (XKYCX19_155).

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  1. Jie Zhang and Yanggang Rui contribute equally to this article.

Authors and Affiliations

  1. Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China

    Jie Zhang, Manman Gao, Li Wang & Bing Chun Yan

  2. Department of Neurology, Affiliated Hospital, Yangzhou University, Yangzhou, 225001, People’s Republic of China

    Jie Zhang & Bing Chun Yan

  3. Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, People’s Republic of China

    Bing Chun Yan

  4. Department of Neurology, Xuyi People’s Hospital, Huai’an, 211700, People’s Republic of China

    Yanggang Rui

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  1. Jie Zhang
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JZ and YGR performed the experiments and drafted the manuscript. MMG and LW analyzed the data; BCY designed the experiments. All the authors discussed the results, reviewed the final manuscript, and approved it for the publication.

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Correspondence to Bing Chun Yan.

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Zhang, J., Rui, Y., Gao, M. et al. Expression of Long Non-coding RNA RGD1566344 in the Brain Cortex of Male Mice After Focal Cerebral Ischemia–Reperfusion and the Neuroprotective Effect of a Non-coding RNA RGD1566344 Inhibitor. Cell Mol Neurobiol 41, 705–716 (2021). https://doi.org/10.1007/s10571-020-00877-4

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