Abstract
The hsa-mir-483 gene, located within the IGF2 locus, transcribes for two mature microRNAs, miR-483-5p and miR-483-3p. This gene, whose regulation is mediated by the the CTNNB1/USF1 complex, shows an independent expression from its host gene IGF2. The miR-483-3p affects the Wnt/β-catenin, the TGF-β, and the TP53 signaling pathways by targeting several genes as CTNNB1, SMAD4, IGF1, and BBC3. Accordingly, miR-483-3p is associated with various tissues specific physiological properties as insulin and melanin production, as well as with cellular physiological functions such as wounding, differentiation, proliferation, and survival. Deregulation of miR-483-3p is observed in different types of cancer, and its overexpression can inhibit the pro-apoptotic pathway induced by the TP53 target effectors. As a result, the oncogenic characteristics of miR-483-3p are linked to the effect of some of the most relevant cancer-related genes, TP53 and CTNNB1, as well as to one of the most important cancer hallmark: the aberrant glucose metabolism of tumor cells. In this review, we summarize the recent findings regarding the miR-483-3p, to elucidate its functional role in physiological and pathological contexts, focusing overall on its involvement in cancer and in the TP53 pathway.
Highlights
MicroRNAs are noncoding RNAs of about 18–28 ribonucleotide lengths, which modulate gene expression by inhibiting their translation or promoting their mRNA degradation [1].MicroRNAs play a critical function in the homeostasis of central cellular processes, and their deregulation in human neoplasm has mainly been proven [2,3,4].The hsa-miR-483 gene is a mammal-conserved microRNA that resides at the 2nd intron of the human insulin growth factor 2 (IGF2) gene at the 11p15.5 chromosome region [5] (Figure 1).The genomic localization of this microRNA is of particular interest
The association of glucose metabolism to the regulation of miR-483-3p is supported by several studies that connect CTNNB1 and upstream stimulatory stimulatorytranscription transcriptionfactor factor11 (USF1) activity to cellular glucose metabolism [56,57,58] and by the fact that miR-483-3p maps at the INS-IGF2 locus, which is involved in the insulin pathway [7,59]
IGF2, β-catenin and TP53 are related to cellular metabolism [95,96], and lipid and glucose metabolisms are impaired in hepatocellular carcinoma (HCC) [97]
Summary
MicroRNAs (miRNAs) are noncoding RNAs of about 18–28 ribonucleotide lengths, which modulate gene expression by inhibiting their translation or promoting their mRNA degradation [1]. Defects in the imprinting of the IGF2 locus are observed in the Beckwith-Wiedemann syndrome, which increases the incidence of pediatric malignancies as nephroblastoma (Wilms’ tumor), hepatoblastoma, and rhabdomyosarcoma [6]. A transgenic mouse model for IGF2 (without including the miR-483 gene) exhibited several features associated with the Beckwith-Wiedemann syndrome without association to any neoplasia [9]. Thehsa-miR-483 hsa-miR-483gene geneencodes encodesfor fortwo twomature maturemiRNAs: miRNAs:miR-483-5p miR-483-5pand andmiR-483-3p. Both are are found foundderegulated deregulated in indifferent differenttypes typesof ofcancer.
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