Non-coding RNA dysregulation in the amygdala region of schizophrenia patients contributes to the pathogenesis of the disease

Transl Psychiatry. 2018 Feb 2;8(1):44. doi: 10.1038/s41398-017-0030-5.

Abstract

Schizophrenia (SCZ) is a neuropsychiatric disorder with a complex genetic etiology. The redundancy of the gene networks underlying SCZ indicates that many gene combinations have the potential to cause a system dysfunction that can manifest as SCZ or a related neurodevelopmental disorder. Recent studies show that small non-coding microRNA (miRNA) and long non-coding RNA (lncRNA) are important factors in shaping these networks and are dynamically regulated by neuronal activation. We investigated the genome-wide transcription profiles of 46 human amygdala samples obtained from 22 SCZ patients and 24 healthy controls. Using RNA sequencing (RNA-seq), we determined lncRNA expression levels in all samples and generated miRNA profiles for 27 individuals (13 cases and 14 controls). Previous studies have identified differentially expressed miRNAs in SCZ, including miR-132, miR-212, and miR-34a/miR-34c. Here we report differential expression of a novel miRNA, miR1307, in SCZ. Notably, miR1307 maps to a locus previously associated with SCZ through GWAS. Additionally, one lncRNA that was overexpressed in SCZ, AC005009.2, also maps to a region previously associated with SCZ based on GWAS and overlapped SCZ-related genes. The results were replicated in a large independent data set of 254 dorsolateral prefrontal cortex samples from the CommonMind consortium. Taken together, these results suggest that miRNA and lncRNAs are important contributors to the pathogenesis of SCZ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amygdala / metabolism*
  • Female
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Prefrontal Cortex / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Schizophrenia / metabolism*
  • Sequence Analysis, RNA / methods*

Substances

  • MIRN1307 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding