Genetic variants in the promoters of let-7 family are associated with an increased risk of major depressive disorder

Liang, Yundan; Zhao, Guimin; Sun, Ruili; Mao, Yuanyi; Li, Gangqin; Chen, Xueyan; Gao, Linbo; Hu, Zeqing

doi:10.1016/j.jad.2015.04.035

Cited by 27 publications

(22 citation statements)

References 42 publications

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“…There is strong evidence that peripheral miRNAs may contribute to the pathophysiology of MDD and antidepressant response. In fact, genetic variants in the promoters of let-7 family have been associated with an increased risk of MDD ( Liang et al, 2015 ). Also, results indicated that, compared to control subjects, let-7d-3p are significantly higher in the serum from the MDD patients compared to healthy controls.…”

Section: Discussionmentioning

confidence: 93%

Lentiviral-mediated let-7d microRNA overexpression induced anxiolytic- and anti-depressant-like behaviors and impaired dopamine D3 receptor expression

Bahí

Dreyer

2018

European Neuropsychopharmacology

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Generalized anxiety and major depression disorders (MDD) are severe debilitating mood disorders whose etiology are not fully understood, but growing evidence indicates that microRNAs (miRNAs) might play a key role in their neuropathophysiological mechanisms. In the current study, we investigate the role of Lethal-7 (let-7d) miRNA, and its direct target dopamine D3 receptor (D3R) gain-of-function, in the hippocampus, in preclinical models of anxiety and depression in mice. For this purpose, we have constructed a lentiviral vector carrying let-7d miRNA and its anxiolytic effect was investigated by employing the open-field (OF) and the elevated plus maze (EPM) tests. The anti-depressant activity was evaluated using the tail suspension and the forced-swim tests (TST & FST). Our results show that let-7d overexpression significantly improved the measures of anxiety in the OF and EPM tests. In addition, let-7d increased the mobility time in the TST and FST. Interestingly, gene expression interaction analysis shows that the D3R mRNA negatively correlates with let-7d expression. In a different set of experiments, we used a tetracycline-inducible (tet-off) lentiviral vector to overexpress D3R to assess its gain-of-function in the hippocampus on anxiety-and depression-like behaviors. In line, we found that in the absence of doxycycline, D3R produced a significant anxiogenic and depressant-like response. Most importantly, these effects were abrogated when mice were fed doxycycline in drinking water. Our results provide the first evidence for an anxiolytic and

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Section: Discussionmentioning

confidence: 93%

Lentiviral-mediated let-7d microRNA overexpression induced anxiolytic- and anti-depressant-like behaviors and impaired dopamine D3 receptor expression

Bahí

Dreyer

2018

European Neuropsychopharmacology

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“…Detailed information was presented as previously described. 23 To improve the accuracy of the genotyping methods, positive control (heterozygote genotype) and negative control (double distilled water) were used in each experiment. All the results were verified by DNA sequencing.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, Xie et al discovered 2 potentially functional polymorphisms (ie, rs10877887 and rs13293512) in the promoter regions of let-7 family, which might affect binding affinity of a predicted transcription factor. 22 More recently, these single nucleotide polymorphisms (SNPs) were reported to be associated with the risk of major depressive disorder, 23 lung cancer, 24 and survival of hepatocellular carcinoma. 22 To date, little is known about the polymorphisms with IA risk.…”

Section: Introductionmentioning

confidence: 99%

A Potential Polymorphism in the Promoter of Let-7 is Associated With an Increased Risk of Intracranial Aneurysm

et al. 2015

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Let-7 family plays a key role in the progression of atherosclerosis and intracranial aneurysm (IA). We hypothesized that rs10877887 and rs13293512 polymorphisms in the promoters of let-7 family may be associated with the susceptibility of IA. We genotyped the 2 single nucleotide polymorphisms (SNPs) in 305 patients with IA and 401 healthy controls. The rs10877887 was analyzed using a polymerase chain reaction-restriction fragment length polymorphism assay, and the rs13293512 was analyzed using a TaqMan SNP genotyping method. The relative expression of let-7 family was measured in plasma of cases and controls using real-time PCR. We found that the rs13293512CT genotype was associated with a significantly increased risk of developing IA in a heterozygote comparison (adjusted OR = 1.43, 95% CI, 1.00–2.05, P = 0.048) and dominant comparison (adjusted OR = 1.44, 95% CI, 1.02–2.03, P = 0.04). Combined analysis showed that the rs10877887TT and rs13293512CC/CT genotypes had a significantly increased risk of IA (OR = 1.67, 95% CI, 1.04–2.68, P = 0.03). Moreover, the levels of let-7a, let-7d, and let-7f were downregulated in IA patients, and patients with the rs13293512CC/CT genotypes had a lower level of let-7a than those with rs13293512TT genotype (P = 0.03). These findings indicate that the rs13293512CC/CT is a risk factor for the development of IA, possibly because of the genotypes resulting in a lower level of let-7a.

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“… 14 , 15 Xie et al 16 found that the rs10877887 was associated with survival of hepatocellular carcinoma. Liang et al 17 demonstrated that the rs10877887 and rs13293512 had correlation with the susceptibility of major depressive disorder. To date, however, no analyses have been conducted to assess the association between the 2 polymorphisms and PTC risk.…”

Section: Introductionmentioning

confidence: 99%

Association Between Genetic Polymorphisms in the Promoter Regions of Let-7 and Risk of Papillary Thyroid Carcinoma

et al. 2015

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The aim of this study was to investigate the association between 2 polymorphisms (ie, rs10877887 and rs13293512) in the promoter regions of let-7 and the risk of papillary thyroid carcinoma (PTC).A case-control study of 618 PTC patients and 562 controls was conducted. The rs10877887 polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism and the rs13293512 polymorphism was genotyped by using a TaqMan Genotyping Assay. The results were confirmed by DNA sequencing.The rs10877887 polymorphism had reduced risks of PTC in heterozygous comparison, dominant model, and overdominant model (TC vs TT: adjusted odds ratio [OR] = 0.73, 95% confidence interval [95% CI] = 0.58–0.94, P = 0.01; TC/CC vs TT: adjusted OR = 0.79, 95% CI = 0.63–1.00, P = 0.047; TC vs TT/CC: adjusted OR = 0.73, 95% CI = 0.57–0.92, P = 0.007, respectively). Stratified analyses showed that PTC patients carrying the rs10877887 CC genotype were more likely to have multiple tumors (adjusted OR = 1.71, 95% CI = 1.03–2.86, P = 0.04), and PTC patients carrying the rs13293512 TC + CC or CC were more likely to develop N0 status (TC/CC vs TT: adjusted OR = 0.64, 95% CI = 0.43–0.94, P = 0.02; CC vs TC/TT: adjusted OR = 0.50, 95% CI = 0.33–0.77, P = 0.001, respectively).Our study suggests that the rs10877887 polymorphism may be associated with the risk of PTC and the rs13293512 polymorphism may correlate to lymph node metastasis in PTC.

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Genetic variants in the promoters of let-7 family are associated with an increased risk of major depressive disorder

Cited by 27 publications

References 42 publications

Lentiviral-mediated let-7d microRNA overexpression induced anxiolytic- and anti-depressant-like behaviors and impaired dopamine D3 receptor expression

Lentiviral-mediated let-7d microRNA overexpression induced anxiolytic- and anti-depressant-like behaviors and impaired dopamine D3 receptor expression

A Potential Polymorphism in the Promoter of Let-7 is Associated With an Increased Risk of Intracranial Aneurysm

Association Between Genetic Polymorphisms in the Promoter Regions of Let-7 and Risk of Papillary Thyroid Carcinoma

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