The Important Role of Sex-Related Sox Family Genes in the Sex Reversal of the Chinese Soft-Shelled Turtle (Pelodiscus sinensis)

The Chinese soft-shelled turtle Pelodiscus sinensis shows obvious sexual dimorphism. The economic and nutrition value of male individuals are significantly higher than those of female individuals. Pseudo-females which are base to all-male breeding have been obtained by estrogen induction, while the gene function and molecular mechanism of sex reversal remain unclear in P. sinensis. Here, comparative transcriptome analyses of female, male, and pseudo-female gonads were performed, and 14,430 genes differentially expressed were identified in the pairwise comparison of three groups. GO and KEGG analyses were performed on the differentially expressed genes (DEGs), which mainly concentrated on steroid hormone synthesis. Furthermore, the results of gonadal transcriptome analysis revealed that 10 sex-related sox genes were differentially expressed in males vs. female, male vs. pseudo-female, and female vs. pseudo-female. Through the differential expression analysis of these 10 sox genes in mature gonads, six sox genes related to sex reversal were further screened. The molecular mechanism of the six sox genes in the embryo were analyzed during sex reversal after E2 treatment. In mature gonads, some sox family genes, such as sox9sox12, and sox30 were highly expressed in the testis, while sox1, sox3, sox6, sox11, and sox17 were lowly expressed. In the male embryos, exogenous estrogen can activate the expression of sox3 and inhibit the expression of sox8, sox9, and sox11. In summary, sox3 may have a role in the process of sex reversal from male to pseudo-female, when sox8 and sox9 are inhibited. Sox family genes affect both female and male pathways in the process of sex reversal, which provides a new insight for the all-male breeding of the Chinese soft-shelled turtle.

Identification of SOX6 and SOX12 as Prognostic Biomarkers for Clear Cell Renal Cell Carcinoma: A Retrospective Study Based on TCGA Database

Background. The SOX gene family has been proven to display regulatory effects on numerous diseases, particularly in the malignant progression of neoplasms. However, the molecular functions and action mechanisms of SOX genes have not been clearly elucidated in clear cell renal cell carcinoma (ccRCC). We aimed to explore the expression status, prognostic values, clinical significances, and regulatory actions of SOX genes in ccRCC. Methods. RNA-sequence data and clinical information derived from The Cancer Genome Atlas (TCGA) database was used for this study. Dysregulated SOX genes between the normal group and ccRCC group were screened using the Wilcoxon signed-rank test. The Kaplan-Meier analysis and univariate Cox analysis methods were used to estimate the overall survival (OS) and disease-specific survival (DSS) differences between different groups. The independent prognostic factors were identified by the use of uni- and multivariate assays. Subsequently, the Wilcoxon signed-rank test or Kruskal-Wallis test and the chi-square test or Fisher exact probability methods were employed to explore the association between clinicopathological variables and SOX genes. Finally, CIBERSORT was applied to study the samples and examine the infiltration of immune cells between different groups. Results. Herein, 12 dysregulated SOX genes in ccRCC were screened. Among them, two independent prognostic SOX genes (SOX6 and SOX12) were identified. Further investigation results showed that SOX6 and SOX12 were distinctly associated with clinicopathological features. Furthermore, functional enrichment analysis revealed that SOX6 and SOX12 were enriched in essential biological processes and signaling pathways. Finally, we found that the SOX6 and SOX12 expression levels were correlated with tumor-infiltrating immune cells (TIICs). Conclusion. The pooled analyses showed that SOX6 and SOX12 could serve as promising biomarkers and therapeutic targets of patients with ccRCC.

Editing SOX Genes by CRISPR-Cas: Current Insights and Future Perspectives

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and its associated proteins (Cas) is an adaptive immune system in archaea and most bacteria. By repurposing these systems for use in eukaryote cells, a substantial revolution has arisen in the genome engineering field. In recent years, CRISPR-Cas technology was rapidly developed and different types of DNA or RNA sequence editors, gene activator or repressor, and epigenome modulators established. The versatility and feasibility of CRISPR-Cas technology has introduced this system as the most suitable tool for discovering and studying the mechanism of specific genes and also for generating appropriate cell and animal models. SOX genes play crucial roles in development processes and stemness. To elucidate the exact roles of SOX factors and their partners in tissue hemostasis and cell regeneration, generating appropriate in vitro and in vivo models is crucial. In line with these premises, CRISPR-Cas technology is a promising tool for studying different family members of SOX transcription factors. In this review, we aim to highlight the importance of CRISPR-Cas and summarize the applications of this novel, promising technology in studying and decoding the function of different members of the SOX gene family.

Multi-Omics Analysis of SOX4, SOX11, and SOX12 Expression and the Associated Pathways in Human Cancers

The Sry-related HMG BOX (SOX) gene family encodes transcription factors containing highly conserved high-mobility group domains that bind to the minor groove in DNA. Although some SOX genes are known to be associated with tumorigenesis and cancer progression, their expression and prognostic value have not been systematically studied. We performed multi-omic analysis to investigate the expression of SOX genes in human cancers. Expression and phylogenetic tree analyses of the SOX gene family revealed that the expression of three closely related SOX members, SOX4, SOX11, and SOX12, was increased in multiple cancers. Expression, mutation, and alteration of the three SOX members were evaluated using the Oncomine and cBioPortal databases, and the correlation between these genes and clinical outcomes in various cancers was examined using the Kaplan–Meier, PrognoScan, and R2 database analyses. The genes commonly correlated with the three SOX members were categorized in key pathways related to the cell cycle, mitosis, immune system, and cancer progression in liver cancer and sarcoma. Additionally, functional protein partners with three SOX proteins and their probable signaling pathways were explored using the STRING database. This study suggests the prognostic value of the expression of three SOX genes and their associated pathways in various human cancers.

Differential Expression of Members of SOX Family of Transcription Factors in Failing Human Hearts

Background: The Sry-related high-mobility-group box (SOX) gene family, with 20 known transcription factors in humans, plays essential roles during development and in many disease processes. Several SOX proteins, e.g., SOX4, SOX11, and SOX9, are required for normal heart morphogenesis. SOX9 was shown to contribute to cardiac fibrosis in animal models. However, differential expression of other SOX transcription factors and their functional roles in the failing human myocardium have not been explored.Methods and Findings: All 20 SOX genes from RNA-seq data were extracted, and their RNA levels were compared to the NF, DCM, and hypertrophic cardiomyopathy (HCM) groups. The protein levels of the differential expressed SOX genes were confirmed by Western blot. Four SOX genes whose RNA levels were significantly upregulated in DCM or HCM compared to NF. However, only SOX4 and SOX8 proteins were markedly increased in the heart failure groups. Gene co-expression network analysis identified genes associated and respond similarly to perturbations with SOX4 in cardiac tissues. Using a meta-analysis combining epigenetics and genome-wide association data, we reported several genomic variants associated with HF phenotype linked to SOX4 or SOX8.Conclusions: Elevation of SOX8 and SOX4 are observed in the failing human myocardium. The molecular mechanism associated with them in HF warrants further investigation.

The evolution of Sox gene repertoires and regulation of segmentation in arachnids

The Sox family of transcription factors regulate many different processes during metazoan development, including stem cell maintenance, nervous system specification and germline development. In addition, it has recently become apparent that SoxB genes are involved in embryonic segmentation in several arthropod species. Segmentation in arthropods occurs in two main ways: long germ animals form all segments at once, best exemplified in the well-studied Drosophila melanogaster system, and short germ animals form anterior segments simultaneously, with posterior segments added sequentially from a segment addition zone. In both D. melanogaster and the short germ beetle Tribolium castaneum, the SoxB gene Dichaete is required for correct segmentation and, more recently, we showed that a close relative of Dichaete, Sox21b-1, is required for the simultaneous formation of prosomal segments and sequential addition of opisthosomal segments in the spider Parasteatoda tepidariorum. Here we further analysed the function and expression of Sox21b-1 in P. tepidariorum. We found that while this gene regulates the generation of both prosomal and opisthosomal segments, it plays different roles in the formation of these tagma reflecting their contrasting modes of segmentation and deployment of gene regulatory networks with different architectures. To further investigate the evolution of Sox genes and their roles we characterised the repertoire of the gene family across several arachnid species with and without an ancestral whole genome duplication, and compared Sox expression between P. tepidariorum and the harvestman Phalangium opilio. The results suggest that Sox21b-1 was likely involved in segmentation ancestrally in arachnids, but that other Sox genes could also regulate this process in these animals. We also found that most Sox families have been retained as duplicates or ohnologs after WGD and evidence for potential subfunctionalisation and/or neofunctionalization events.