AUTHOR=Kazerani Reihane , Salehipour Pouya , Shah Mohammadi Mohammadreza , Amanzadeh Jajin Elnaz , Modarressi Mohammad Hossein 

TITLE=Identification of TSGA10 and GGNBP2 splicing variants in 5′ untranslated region with distinct expression profiles in brain tumor samples

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1075638

DOI=10.3389/fonc.2023.1075638

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>Brain tumors (BTs) are perceived as one of the most common malignancies among children. The specific regulation of each gene can play a critical role in cancer progression. The present study aimed to determine the transcripts of the <italic>TSGA10</italic> and <italic>GGNBP2</italic> genes, considering the alternative 5′UTR region, and investigating the expression of these different transcripts in BTs.</p></sec><sec><title>Material and methods</title><p>Public data on brain tumor microarray datasets in GEO were analyzed with R software to evaluate the expression levels of <italic>TSGA10</italic> and <italic>GGNBP2</italic> genes (the Pheatmap package in R was also used to plot DEGs in a heat map). In addition, to validate our in-silico data analysis, RT-PCR was performed to determine the splicing variants of <italic>TSGA10</italic> and <italic>GGNBP2</italic> genes in testis and brain tumor samples. The expression levels of splice variants of these genes were analyzed in 30 brain tumor samples and two testicular tissue samples as a positive control.</p></sec><sec><title>Results</title><p>In silico results show that the differential expression levels of <italic>TSGA10</italic> and <italic>GGNBP2</italic> were significant in the GEO datasets of BTs compared to normal samples (with adjusted p-value&lt;0.05 and log fold change &gt; 1). This study’s experimental results showed that the <italic>TSGA10</italic> gene produces four different transcripts with two distinct promoter regions and splicing exon 4. The relative mRNA expression of transcripts without exon 4 was higher than transcripts with exon 4 in BT samples (p-value&lt;001). In <italic>GGNBP2</italic>, exon 2 in the 5′UTR region and exon 6 in the coding sequence were spliced. The expression analysis results showed that the relative mRNA expression of transcript variants without exon 2 was higher than other transcript variants with exon 2 in BT samples (p-value&lt;001).</p></sec><sec><title>Conclusion</title><p>The decreased expression levels of transcripts with longer 5′UTR in BT samples than in testicular or low-grade brain tumor samples may decrease their translation efficiency. Therefore, decreased amounts of TSGA10 and GGNBP2 as potential tumor suppressor proteins, especially in high-grade brain tumors, may cause cancer development by angiogenesis and metastasis.</p></sec>