Altered expression levels of miR-144-3p and ATP1B2 are associated with schizophrenia

Abstract

Objectives: Schizophrenia is a devastating mental disease. Various microRNAs were proven to be associated with schizophrenia. Altered microRNA-144-3p (miR-144-3p) levels were found in various neurological and psychotic disorders. Beta2-subunit of Na(+)/K(+)-ATPase (ATP1B2) regulates neuronal migration and cell growth during brain development through the PI3K/Akt/mTOR pathway. The present study explored the associations of miR-144-3p and ATP1B2 with schizophrenia and their mutual interaction.

Methods: A schizophrenic animal model employing repeated MK-801 administration was established and 293 T cells over-expressing miR-144-3p were constructed by lentivirus. The in vitro and in vivo levels of miR-144-3p, ATP1B2, and the PI3K/Akt/mTOR pathway were examined by qRT-PCR and Western Blots. The interaction between miR-144-3p and ATP1B2 was predicted and assessed by using bioinformatic methods and a luciferase reporter gene assay, respectively.

Results: MiR-144-3p expression was elevated in the schizophrenic rat hippocampus. ATP1B2 was down-regulated in schizophrenic patients by analysing GEO datasets. Additionally, miR-144-3p can directly bind with ATP1B2. Furthermore, the ATP1B2 expression and PI3K/Akt/mTOR phosphorylation levels were down-regulated in the 293 T cells over-expressing miR-144-3p and schizophrenic rat hippocampus, which could be reversed by risperidone.

Conclusions: This study revealed that up-regulated miR-144-3p might be associated with schizophrenia through down-regulating ATP1B2, implicating new targets of schizophrenia treatment.

Keywords:

• Schizophrenia
• microRNA-144-3p
• ATP1B2
• PI3K/Akt/mTOR signalling pathway
• risperidone

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the China Postdoctoral Science Foundation [2018M632401] and Yangzhou Scientific and Technological Development Program [YZ2019063]. The funding organisation did not play a role in study design and conduct, data interpretation, or paper writing.