Let-7, mir-98 and mir-183 as biomarkers for cancer and schizophrenia [corrected].

Recent evidence supports a role of microRNAs in cancer and psychiatric disorders such as schizophrenia and bipolar disorder, through their regulatory role on the expression of multiple genes. The rather rare co-morbidity of cancer and schizophrenia is an old hypothesis which needs further research on microRNAs as molecules that might exert their oncosuppressive or oncogenic activity in the context of their role in psychiatric disorders. The expression pattern of a variety of different microRNAs was investigated in patients (N = 6) suffering from schizophrenia termed control, patients with a solid tumor (N = 10) and patients with both schizophrenia and tumor (N = 8). miRNA profiling was performed on whole blood samples using the miRCURY LNA microRNA Array technology (6th & 7th generation). A subset of 3 microRNAs showed a statistically significant differential expression between the control and the study groups. Specifically, significant down-regulation of the let-7p-5p, miR-98-5p and of miR-183-5p in the study groups (tumor alone and tumorand schizophrenia) was observed (p<0.05). The results of the present study showed that let-7, miR-98 and miR-183 may play an important oncosuppressive role through their regulatory impact in gene expression irrespective of the presence of schizophrenia, although a larger sample size is required to validate these results. Nevertheless, further studies are warranted in order to highlight a possible role of these and other micro-RNAs in the molecular pathways of schizophrenia

Control and Study groups of the study.

<p>No statistically significant difference was found between the mean ages of the control and the study groups (student's t-test, <i>p</i> = 0.36).</p

Heat map diagram showing the expression of the 50 miRNAs with the highest standard deviation in all samples.

<p>The color scale illustrates the relative expression level of miRNAs and specifically, red color represents an expression level below the reference channel, whereas green color represents an expression higher than the reference. Each row represents a microRNA and each column represents a sample. The microRNA clustering tree is shown on the left. The control and study groups are clearly indicated with different colours. Samples S9-S13, S16, S18 & S19 correspond to the study group of patients with schizophrenia and tumor formation, whereas samples S21-S30 correspond to the study group of patients with tumor formation only. The 3 miRNAs, the expression of which was found to be significantly higher in the samples of the control group of patients, are also indicated.</p

PCA plot of the different sample classes.

<p>The principal component analysis was performed on all samples, and on the top 50 microRNAs with the highest standard deviation. The normalized log ratio values have been used for the analysis. The features have been shifted to be zero centered, (i.e. the mean value across samples is shifted to 0) and scaled to have unit variance (i.e. the variance across samples is scaled to 1) before the analysis. Samples C2-C5, C7 & C13 correspond to the control group of patients, whereas sample codes beginning with S correspond to the 2 subsets of the study group, designated and colored separately as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123522#pone.0123522.g002" target="_blank">Fig 2</a>.</p