Abstract
PRDM12 is a member of the PRDI-BF1 (positive regulatory domain I-binding factor 1) homologous domain (PRDM)-containing protein family, a subfamily of Kruppel-like zinc finger proteins, controlling key processes in the development of cancer. PRDM12 is expressed in a spatio-temporal manner in neuronal systems where it exerts multiple functions. PRDM12 is essential for the neurogenesis initiation and activation of a cascade of downstream pro-neuronal transcription factors in the nociceptive lineage. PRDM12 inactivation, indeed, results in a complete absence of the nociceptive lineage, which is essential for pain perception. Additionally, PRDM12 contributes to the early establishment of anorexigenic neuron identity and the maintenance of high expression levels of pro-opiomelanocortin, which impacts on the program bodyweight homeostasis. PRDMs are commonly involved in cancer, where they act as oncogenes/tumor suppressors in a “Yin and Yang” manner. PRDM12 is not usually expressed in adult normal tissues but its expression is re-activated in several cancer types. However, little information is currently available on PRDM12 expression in cancers and its mechanism of action has not been thoroughly described. In this review, we summarize the recent findings regarding PRDM12 by focusing on four main biological processes: neurogenesis, pain perception, oncogenesis and cell metabolism. Moreover, we wish to highlight the importance of future studies focusing on the PRDM12 signaling pathway(s) and its role in cancer onset and progression.
Highlights
Both the PR and zinc-finger domains of Prdm12 were required to exert this function; Prdm12 may act as a G9a-dependent repressor to induce En1. This activity was not found in the amphioxus, and differences in the C-terminal region of the protein, including the zinc-finger domains, may account for the differential functions of the amphioxus and vertebrate proteins. These findings indicated that Prdm12 could promote V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes
Our pan-cancer meta-analysis based on The Cancer Genome Atlas (TCGA) data showed that PRDM12 was upregulated in several cancer types: colon, breast, kidney, colon, lung, liver, thyroid, ovary and prostate cancers, suggesting that it could represent a putative tumor marker [25]
Neuronal cell fate specification is orchestrated by several fine-tuned molecular mechaNeuronal cell fate specification is orchestrated by several fine-tuned molecular nisms in which several transcription factors are involved
Summary
Most PRDM genes express two main molecular variants, with one lacking the PR domain These two isoforms, which can be generated by either alternative splicing or the alternative use of different promoters, play opposite roles in cancer [1,25,26]. We summarize the current knowledge on PRDM12 gene functions by dissecting their involvement in four main processes: neurogenesis, pain perception, cell metabolism. We summarize the current knowledge on PRDM12 gene functions by of 15 dissecting their involvement in four main processes: neurogenesis, pain perception, 3cell metabolism and oncogenesis (see graphical abstract) [22,31]. The human PRDM12 gene is localized on chromosome 9 at 9q33-q34, according to the
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