Identification of Antisense lncRNAs Targeting GSK3β as a Regulator in Major Depressive Disorder

Abstract

Aim: To identify lncRNAs targeting GSK3β in MDD. Materials & methods: The levels of GSK3β and its three targeting lncRNAs (gsk3β antisense AS1, AS2 and AS3) were detected in 52 patients with major depressive disorder (MDD) before and after 8 weeks of escitalopram treatment. The functional study was evaluated using the silence of lncR-gsk3βAS2/3. The correlation between lncRNA-gsk3β and 89 MDD patients was analyzed. Human neuron progenitor cells were used to investigate the functional role of lncRNA-gsk3β in MDD. Results: All three lncRNAs were downregulated in MDD patients but upregulated after treatment. Inhibition of gsk3βAS2/3 reduced GSK3β expression and its phosphorylation levels in the neuron progenitor cells. Conclusion: Our findings suggest that lncRNA-gsk3βAS3 regulates GSK3β activity in MDD and has potential as a novel therapeutic target.

Keywords: :

• antidepressant strategy
• GSK3β
• lncRNA
• major depressive disorder
• neuroplasticity

Acknowledgments

We would like to show our deepest gratitude to Liu Hailiang, from Tongji University, Shanghai, who has provided a lot of help for the experiments. We also extend our thanks to Liu Sha and Cao Xiaohua, from the First Hospital of Shanxi Medical University, who helped us to collect samples.

Financial & competing interests disclosure

This work was supported by grants from National Science Foundation of China [grant 81601193 and 81471379], Peking, China; Shanxi Province Key Research and Development Project (International Cooperation) [grant 201903D421059], Taiyuan, China; Shanxi Province Science Foundation for Youths [grant 2015021204], Taiyuan, China; Research Project Supported by Shanxi Scholarship Council of China [grant 2015-100], Taiyuan, China; The First Hospital of Shanxi Medical University Foundation for Youths Innovation [grant YC1409], Taiyuan, China. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

This manuscript utilized writing assistance from CureEdit (a professional English editorial service company). The source of funding for this service is National Science Foundation of China [grant 81601193], Peking, China.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by grants from National Science Foundation of China [grant 81601193 and 81471379], Peking, China; Shanxi Province Key Research and Development Project (International Cooperation) [grant 201903D421059], Taiyuan, China; Shanxi Province Science Foundation for Youths [grant 2015021204], Taiyuan, China; Research Project Supported by Shanxi Scholarship Council of China [grant 2015-100], Taiyuan, China; The First Hospital of Shanxi Medical University Foundation for Youths Innovation [grant YC1409], Taiyuan, China. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This manuscript utilized writing assistance from CureEdit (a professional English editorial service company). The source of funding for this service is National Science Foundation of China [grant 81601193], Peking, China.