Flavin Adenine Dinucleotide (FAD) and Pyridoxal 5'-Phosphate (PLP) Bind to Sox9 and Alter the Expression of Key Pancreatic Progenitor Transcription Factors.

Cofactor flavin adenine dinucleotide (FAD), a compound with flavin moiety and a derivative of riboflavin (vitamin B2), is shown to bind to Sox9 (a key transcription factor in early pancreatic development) and, subsequently, induce a large increase in markers of pancreatic development, including Ngn3 and PTF1a. Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, also binds to Sox9 and results in a similar increase in pancreatic development markers. Sox9 is known to be specifically important for pancreatic progenitors. Previously, there was no known link between FAD, PLP, or other co-factors and Sox9 for function. Thus, our findings show the mechanism by which FAD and PLP interact with Sox9 and result in the altered expression of pancreatic progenitor transcription factors involved in the pancreas development.

The role of SOX family members in solid tumours and metastasis.

Cancer is a heavy burden for humans across the world with high morbidity and mortality. Transcription factors including sex determining region Y (SRY)-related high-mobility group (HMG) box (SOX) proteins are thought to be involved in the regulation of specific biological processes. The deregulation of gene expression programs can lead to cancer development. Here, we review the role of the SOX family in breast cancer, prostate cancer, renal cell carcinoma, thyroid cancer, brain tumours, gastrointestinal and lung tumours as well as the entailing therapeutic implications. The SOX family consists of more than 20 members that mediate DNA binding by the HMG domain and have regulatory functions in development, cell-fate decision, and differentiation. SOX2, SOX4, SOX5, SOX8, SOX9, and SOX18 are up-regulated in different cancer types and have been found to be associated with poor prognosis, while the up-regulation of SOX11 and SOX30 appears to be favourable for the outcome in other cancer types. SOX2, SOX4, SOX5 and other SOX members are involved in tumorigenesis, e.g. SOX2 is markedly up-regulated in chemotherapy resistant cells. The SoxF family (SOX7, SOX17, SOX18) plays an important role in angio- and lymphangiogenesis, with SOX18 seemingly being an attractive target for anti-angiogenic therapy and the treatment of metastatic disease in cancer. In summary, SOX transcription factors play an important role in cancer progression, including tumorigenesis, changes in the tumour microenvironment, and metastasis. Certain SOX proteins are potential molecular markers for cancer prognosis and putative potential therapeutic targets, but further investigations are required to understand their physiological functions.

Genome-wide analysis of the Chinese sturgeon sox gene family: identification, characterisation and expression profiles of different tissues.

The sox family is assumed to be responsible for a number of developmental systems. Genome sequencing technology makes it possible to scan sox genes and conduct characteristic analyses of different species. In fish, full characterisation of sox genes at the genome-wide level has been reported for pufferfish Takifugu rubripes, medaka Oryzias latipes, tilapia Oreochromis niloticus and channel catfish Ictalurus punctatus. However, no systematic investigation of the sox family in sturgeons (Acipenseridae) has been reported to date. This study conducted genome-wide identification of the sox genes in the Chinese sturgeon Acipenser sinensis and profiled their tissue distribution between male and female individuals. In total, 19 sox genes were identified, including soxb1, b2, c, d, e, f and h, in the Chinese sturgeon. Genomic structure analysis indicated relatively conserved exon-intron structures in each sox group and phylogenetic analysis supported the previous classification of the sox family. Most of the sox genes showed a tissue-specific expression pattern, indicating the possible involvement of Chinese sturgeon sox genes at different developmental processes such as cardiac and gonadal development. This study provides a comprehensive resource of Chinese sturgeon sox genes and enables a better understanding of the evolution and function of the sox family.

SOX family transcription factors as therapeutic targets in wound healing: A comprehensive review.

The SOX family plays a vital role in determining the fate of cells and has garnered attention in the fields of cancer research and regenerative medicine. It also shows promise in the study of wound healing, as it actively participates in the healing processes of various tissues such as skin, fractures, tendons, and the cornea. However, our understanding of the mechanisms behind the SOX family's involvement in wound healing is limited compared to its role in cancer. Gaining insight into its role, distribution, interaction with other factors, and modifications in traumatized tissues could provide valuable new knowledge about wound healing. Based on current research, SOX2, SOX7, and SOX9 are the most promising members of the SOX family for future interventions in wound healing. SOX2 and SOX9 promote the renewal of cells, while SOX7 enhances the microvascular environment. The SOX family holds significant potential for advancing wound healing research. This article provides a comprehensive review of the latest research advancements and therapeutic tools related to the SOX family in wound healing, as well as the potential benefits and challenges of targeting the SOX family for wound treatment.

Integrative analysis of the SOX family-related prognostic signature and immunological infiltration in prostate cancer.

Background: Prostate cancer (PCa) remains a major prevalent cancer worldwide and has a poor prognosis. The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family is a series of transcription factors (TFs) involved in regulating many biological processes (BPs). In tumors, however, SOX genes are frequently deregulated. Tumorigenic deregulation took place at the transcriptional, translational, and posttranslational levels. This leads them to be correlated to tumor progression and poor clinical outcomes in PCa. Nevertheless, the SOX family prognostic role in PCa still needs further investigation. Methods: A SOX family-related prognostic signature was developed by performing LASSO (Least absolute shrinkage and selection operator) Cox regression analysis. The construction of a lncRNA-miRNA-mRNA regulatory axis for PCa was performed using a ceRNA network. Results: Upregulation was observed in the expression of SOX4/8/11/12/14, while downregulation was observed for SOX2/5/7/13/15/30 in PCa. Consensus clustering identified four clusters of PCa patients based on these differentially expressed SOX family members. The constructed SOX family-related prognostic signature, which includes five SOX family members (SOX5/8/11/12/30), performed well in predicting PCa-patient prognosis. B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cell immune infiltration levels had a significant association with PCa-patient risk scores. Based on additional analysis, a significant association was also suggested between SOX family expression and tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity. By constructing a ceRNA network, a lncRNA SGMS1-AS1/miR-194-5p/SOX5 regulatory axis was developed for PCa. Conclusions: Herein, a SOX family-related prognostic signature was identified and was found to perform well in predicting PCa-patient prognosis. A lncRNA SGMS1-AS1/miR-194-5p/SOX5 regulatory axis was also identified for PCa progression.

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.

The role of SOX family in cancer stem cell maintenance: With a focus on SOX2.

The role of cancer stem cells (CSCs) in cancer incidence, drug resistance, and relapse after chemotherapy has been discussed and it has been confirmed that CSCs are extremely important and so, are suitable for therapeutic targeting. Sox families play an important role in carcinogenesis and dis-regulation of SOXs molecules has been observed in different types of cancers. The members of this family have been shown to play an important role in the maintenance of CSCs. In this article, we have tried to evaluate the role of different family members in CSCs maintenance, review various studies in this field and provide a perspective view on this issue. Also, due to the important role and many studies in the field of SOX2 molecule in CSCs, we try to have more focus on this molecule and examine the potential of these molecules for therapeutic targeting.

Systematic identification and expression analysis of the Sox gene family in spotted sea bass (Lateolabrax maculatus).

The Sox gene family encodes a set of transcription factors characterized by a conserved Sry-related high mobility group (HMG)-box domain, which performs a series of essential biological functions in diverse tissues and developmental processes. In this study, the Sox gene family was systematically characterized in spotted sea bass (Lateolabrax maculatus). A total of 26 Sox genes were identified and classified into eight subfamilies, namely, SoxB1, SoxB2, SoxC, SoxD, SoxE, SoxF, SoxH and SoxK. The phylogenetic relationship, exon-intron and domain structure analyses supported their annotation and classification. Comparison of gene copy numbers and chromosome locations among different species indicated that except tandem duplicated paralogs of Sox17/Sox32, duplicated Sox genes in spotted sea bass were generated from teleost-specific whole genome duplication during evolution. In addition, qRT-PCR was performed to detect the expression profiles of Sox genes during development and adulthood. The results showed that the expression of 16 out of 26 Sox genes was induced dramatically at different starting points after the multicellular stage, which is consistent with embryogenesis. At the early stage of sex differentiation, 9 Sox genes exhibited sexually dimorphic expression patterns, among which Sox3, Sox19 and Sox6b showed the most significant ovary-biased expression. Moreover, the distinct expression pattern of Sox genes was observed in different adult tissues. Our results provide a fundamental resource for further investigating the functions of Sox genes in embryonic processes, sex determination and differentiation as well as controlling the homeostasis of adult tissues in spotted sea bass.

The role of SOX family transcription factors in gastric cancer.

Gastric cancer (GC) is a leading cause of death worldwide. GC is the third-most common cause of cancer-related death after lung and colorectal cancer. It is also the fifth-most commonly diagnosed cancer. Accumulating evidence has revealed the role of signaling networks in GC progression. Identification of these molecular pathways can provide new insight into therapeutic approaches for GC. Several molecular factors involved in GC can play both onco-suppressor and oncogene roles. Sex-determining region Y (Sry)-box-containing (SOX) family members are transcription factors with a well-known role in cancer. SOX proteins can bind to DNA to regulate cellular pathways via a highly conserved domain known as high mobility group (HMG). In the present review, the roles of SOX proteins in the progression and/or inhibition of GC are discussed. The dual role of SOX proteins as tumor-promoting and tumor-suppressing factors is highlighted. SOX members can affect upstream mediators (microRNAs, long non-coding RNAs and NF-κB) and down-stream mediators (FAK, HIF-1α, CDX2 and PTEN) in GC. The possible role of anti-tumor compounds to target SOX pathway members in GC therapy is described. Moreover, SOX proteins may be used as diagnostic or prognostic biomarkers in GC.

Genome-wide identification and expression profiling of the SOX gene family in a bivalve mollusc Patinopecten yessoensis.

SOX family is composed of transcription factors that play vital roles in various developmental processes. Comprehensive understanding on evolution of the SOX family requires full characterization of SOX genes in different phyla. Mollusca is the second largest metazoan phylum, but till now, systematic investigation on the SOX family is still lacking in this phylum. In this study, we conducted genome-wide identification of the SOX family in Yesso scallop Patinopecten yessoensis and profiled their tissue distribution and temporal expression patterns in the ovaries and testes during gametogenesis. Seven SOX genes were identified, including SOXB1, B2, C, D, E, F and H, representing the first record in protostomes with SOX members identical to that proposed to exist in the last common ancestor of chordates. Genomic structure analysis identified relatively conserved exon-intron structures, accompanied by intron insertion. Quantitative real-time PCR analysis revealed possible involvement of scallop SOX in various functions, including neuro-sensory cell differentiation, hematopoiesis, myogenesis and gametogenesis. This study represents the first systematic characterization of SOX gene family in Mollusca. It will assist in a better understanding of the evolution and function of SOX family in metazoans.

Transcription factors from Sox family regulate expression of zebrafish Gla-rich protein 2 gene.

GRP is a vitamin K-dependent protein with orthologs in all vertebrate taxonomic groups and two paralogs in teleosts. However, no data is available about GRP transcriptional gene regulation. We report a functional promoter for zebrafish grp2 gene regulated by Sox9b, Sox10, Ets1 and Mef2ca as determined by in vitro assays. This was confirmed in vivo for Sox9b and Sox10. Due to the high conservation between human GRP and grp2, its zebrafish ortholog, our results are relevant for the study of human GRP gene regulation and provide new insights towards understanding GRP function.

Research progress of the correlation of Sox 5 and tumor / 基础医学与临床

Sox5 gene is located on 12p12.1 containing 29 exons.The gene can transcript 5 variants, thus produce 5 isoforms.L-SOX5A is an isoform with multiple functions , include regulate embryonic development , and determine cell differentiation .Sox5 also plays a role in pathogenesis of prostate cancer , breast cancer and lymphoma .