社会経済的格差のネガティブな認識と抑うつ気分は末梢血白血球のPPBPとSLC1A7 遺伝子の発現を低下させる

Inequality in socioeconomic status (SES) is associated with an increased risk for the development of mental health problems. Here, we examined the association between socioeconomic status (SSS) and psychological distress, and measured gene expression signatures in peripheral blood leukocytes responsible for this association, in 129 healthy adults (27 males and 102 females, aged 44.0 ± 13.0 years) working in a private hospital in Japan. Depressive mood was assessed by Zung Selfrating Depression Scale (SDS). A multiple regression analysis adjusted for gender and age showed that subjective SSS was independently and negatively associated with SDS score. We next focused on 9 subjects who exhibited low SSS scores and 11 subjects with high SSS scores. Microarray analysis revealed that levels of 522 mRNAs were differentially expressed in periheral leukocytes between low and high-SSS groups. The differentially expressed genes were preferentially involved in cellular movement or inflammatory responses. Among them, mRNA levels of pro-platelet basic protein (PPBP) and solute carrier family 1 (glutamine transporter), member 7 (SLC1A7) were negatively correlated with SSS scores. Our results re-confirmed the association between negative perception of SES and depressive mood in healthy adults, and suggest a possible involvement of PPBP and SLC1A7 in the association

ヌクレオリンは、超保存領域を含むTRA2β4を核内に保持し、大腸がん細胞の増殖を促進する

Transcribed-ultraconserved regions (T-UCRs), which contain conserved sequences with 100% identity across human, rat and mouse species, are a novel category of functional RNAs. The human transformer 2β gene (TRA2B) encodes a UCR that spans exon 2 (276 bp) and its neighboring introns. Among five spliced RNA variants (TRA2β1-5) transcribed from the TRA2B gene, only TRA2β4 contains the conserved exon 2. TRA2β4 is overexpressed in colon cancer cells and accelerates cell growth by blocking the transcription of CDKN1A. However, the mechanisms underlying the overexpression of TRA2β4 in colon cancer cells are unknown. Using biotinylated RNA pull-down assays followed by liquid chromatography-mass spectrometric analysis, we identified nucleolin as a TRA2β4-binding protein. Knockdown of nucleolin reduced the nuclear retention of TRA2β4 and accelerated its degradation in the cytoplasm, whereas nucleolin overexpression increased TRA2β4 levels and its mitogenic activity. Nucleolin directly bound to TRA2β4 exon 2 via the glycine/arginine-rich (GAR) domain. Overexpression of GAR-deficient nucleolin failed to increase TRA2β4 expression and growth of colon cancer cells. RNA fluorescence in situ hybridization showed that TRA2β4 co-localized with nucleolin in nuclei but not with the mutant lacking GAR. Our results suggest that specific interactions between nucleolin and UCR-containing TRA2β4 may be associated with abnormal growth of colon cancer cells

Negative perception of socioeconomic status with depressive mood down-regulates expression of <i>PPBP</i> and <i>SLC1A7</i> genes in peripheral blood leukocytes

<p>Inequality in socioeconomic status (SES) is associated with an increased risk for the development of mental health problems. Here, we examined the association between socioeconomic status (SSS) and psychological distress, and measured gene expression signatures in peripheral blood leukocytes responsible for this association, in 129 healthy adults (27 males and 102 females, aged 44.0 ± 13.0 years) working in a private hospital in Japan. Depressive mood was assessed by Zung Self-rating Depression Scale (SDS). A multiple regression analysis adjusted for gender and age showed that subjective SSS was independently and negatively associated with SDS score. We next focused on 9 subjects who exhibited low SSS scores and 11 subjects with high SSS scores. Microarray analysis revealed that levels of 522 mRNAs were differentially expressed in periheral leukocytes between low and high-SSS groups. The differentially expressed genes were preferentially involved in cellular movement or inflammatory responses. Among them, mRNA levels of <i>pro</i>-<i>platelet basic protein</i> (<i>PPBP</i>) and <i>solute carrier family 1</i> (<i>glutamine transporter</i>), <i>member 7</i> (<i>SLC1A7</i>) were negatively correlated with SSS scores. Our results re-confirmed the association between negative perception of SES and depressive mood in healthy adults, and suggest a possible involvement of <i>PPBP</i> and <i>SLC1A7</i> in the association.</p

Chronic Academic Stress Increases a Group of microRNAs in Peripheral Blood

<div><p>MicroRNAs (miRNAs) play key roles in regulation of cellular processes in response to changes in environment. In this study, we examined alterations in miRNA profiles in peripheral blood from 25 male medical students two months and two days before the National Examination for Medical Practitioners. Blood obtained one month after the examination were used as baseline controls. Levels of seven miRNAs (miR-16, -20b, -26b, -29a, -126, -144 and -144*) were significantly elevated during the pre-examination period in association with significant down-regulation of their target mRNAs (<i>WNT4</i>, <i>CCM2</i>, <i>MAK</i>, and <i>FGFR1</i> mRNAs) two days before the examination. State anxiety assessed two months before the examination was positively and negatively correlated with miR-16 and its target <i>WNT4</i> mRNA levels, respectively. Fold changes in miR-16 levels from two days before to one month after the examination were inversely correlated with those in <i>WNT4</i> mRNA levels over the same time points. We also confirmed the interaction between miR-16 and <i>WNT4</i> 3′UTR in HEK293T cells overexpressing FLAG-tagged <i>WNT4</i> 3′UTR and miR-16. Thus, a distinct group of miRNAs in periheral blood may participate in the integrated response to chronic academic stress in healthy young men.</p></div

WNT4 is an <i>in vivo</i> target for miR-16.

<p>(<b>A</b>) miR-16 sequence and a predicted binding site for miR-16 in <i>WNT4</i> 3′UTR are shown. After HEK293 cells were transfected with 10 nM of control (ctrl) or precursor miR-16 for 48 h, mature miR-16 levels (<b>B</b>) and <i>WNT4</i> mRNA levels (<b>C</b>) were measured by qPCR using <i>RNU48</i> and <i>GAPDH</i> mRNA as endogenous quantity controls. Values are mean ± SD from three independent experiments. ^*Significantly different by ANOVA and Bonferroni test (<i>P</i><0.05) compared with those in control siRNA-treated cells. (<b>D</b>) Schematic representation of the parent reporter plasmid pd2EYFP-N1 and the pd2EYFP-<i>WNT4</i> 3′UTR reporter plasmid containing the <i>WNT4</i> 3′UTR (3481-3905). (<b>E</b>) HEK293 cells were transfected with each reporter plasmid, together with either control (ctrl) or precursor miR-16. Forty-eight hours after transfection, YFP mRNA levels were measured by qPCR using <i>GAPDH</i> mRNA as an endogenous quantity control. Values are mean ± SD from three independent experiments. ^*Significantly different by ANOVA and Bonferroni test (<i>p</i><0.05) compared with those in control siRNA-treated cells. (<b>F</b>) YFP and GAPDH protein levels were measured by Western blot analysis.</p

Time-dependent changes in selected target mRNA levels.

<p>Values are mRNA levels (mean ± SEM, n = 25) standardized by <i>GAPDH</i> mRNA levels.</p>1)<p>Statistical significance was determined by repeated measures ANOVA and Bonferroni post hoc test (<i>p</i><0.05).</p

qPCR validation of time-dependent changes in seven miRNA levels.

<p>Time-dependent changes in miR-16 (A), miR-20b (B), miR-26 (C), miR-126 (D), miR-144 (E), miR-144* (F), and miR-29a (G) levels were measured by qPCR using <i>RNU48</i> as endogenous quantity control. Values are mean ± SEM (<i>n</i> = 25). *In the graphs, significantly different by repeated measured ANOVA and Bonferroni post hoc test (<i>p</i><0.05).</p

Examination stress-responsive miRNAs identified by miRNA array.

<p>Values indicate fluorescence intensities (mean ± SEM, n = 4).</p>1)<p><i>P</i>-values were calculated by repeated measures ANOVA.</p>2)<p>Significantly different by Tukey’s post hoc test (<i>p</i><0.05).</p