Identification of Differentially Expressed mRNAs and miRNAs and Related Regulatory Networks in Cumulus Oophorus Complexes Associated with Fertilization

Wang, Caizhu; Zhao, Xin; Wu, Zhulian; Huang, Guiting; Lin, Ruoyun; Chen, Huanhua; Xu, Kongrong; Sun, Kejian; Zhou, Hong; Shu, Jinhui

doi:10.1007/s43032-023-01413-7

Cited by 1 publication

(1 citation statement)

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“…MicroRNAs have long been known to fine-tune gene expression at the post-transcriptional level, giving rise to complex gene regulatory networks [36]. Recently, various novel mechanisms have emerged that further modulate the interaction between microRNAs and their cognate target sequences, including polymorphisms in miRNA target sequences in 3 ′ gene regulatory regions [37], polymorphisms affecting the primary sequence of mi-croRNAs [37,38], sequestration of microRNAs by non-coding circular RNAs [39], and endogenous sponging of microRNAs by the presence of alternative binding sites in target genes [40].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-Mediated Suppression of Glial Cell Line-Derived Neurotrophic Factor Expression Is Modulated by a Schizophrenia-Associated Non-Coding Polymorphism

Keszler,

Vékony,

Elek

et al. 2024

IJMS

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Plasma levels of glial cell line-derived neurotrophic factor (GDNF), a pivotal regulator of differentiation and survival of dopaminergic neurons, are reportedly decreased in schizophrenia. To explore the involvement of GDNF in the pathogenesis of the disease, a case–control association analysis was performed between five non-coding single nucleotide polymorphisms (SNP) across the GDNF gene and schizophrenia. Of them, the ‘G’ allele of the rs11111 SNP located in the 3′ untranslated region (3′-UTR) of the gene was found to associate with schizophrenia. In silico analysis revealed that the rs11111 ‘G’ allele might create binding sites for three microRNA (miRNA) species. To explore the significance of this polymorphism, transient co-transfection assays were performed in human embryonic kidney 293T (HEK293T) cells with a luciferase reporter construct harboring either the ‘A’ or ‘G’ allele of the 3′-UTR of GDNF in combination with the hsa-miR-1185-1-3p pre-miRNA. It was demonstrated that in the presence of the rs11111 ‘G’ (but not the ‘A’) allele, hsa-miR-1185-2-3p repressed luciferase activity in a dose-dependent manner. Deletion of the miRNA binding site or its substitution with the complementary sequence abrogated the modulatory effect. Our results imply that the rs11111 ‘G’ allele occurring more frequently in patients with schizophrenia might downregulate GDNF expression in a miRNA-dependent fashion.

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