Forkhead Box Gene Research Articles

The Forkhead Box Gene, MaSep1, Negatively Regulates UV- and Thermo-Tolerances and Is Required for Microcycle Conidiation in Metarhizium acridum.

Insect pathogenic fungi have shown great potential in agricultural pest control. Conidiation is crucial for the survival of filamentous fungi, and dispersal occurs through two methods: normal conidiation, where conidia differentiate from mycelium, and microcycle conidiation, which involves conidial budding. The conidiation process is related to cell separation. The forkhead box gene Sep1 in Schizosaccharomyces pombe plays a crucial role in cell separation. Nevertheless, the function of Sep1 has not been clarified in filamentous fungi. Here, MaSep1, the homolog of Sep1 in Metarhizium acridum, was identified and subjected to functional analysis. The findings revealed that conidial germination of the MaSep1-deletion strain (ΔMaSep1) was accelerated and the time for 50% germination rate of conidial was shortened by 1 h, while the conidial production of ΔMaSep1 was considerably reduced. The resistances to heat shock and UV-B irradiation of ΔMaSep1 were enhanced, and the expression of some genes involved in DNA damage repair and heat shock response was significantly increased in ΔMaSep1. The disruption of MaSep1 had no effect on the virulence of M. acridum. Interestingly, ΔMaSep1 conducted the normal conidiation on the microcycle conidiation medium, SYA. Furthermore, 127 DEGs were identified by RNA-Seq between the wild-type and ΔMaSep1 strains during microcycle conidiation, proving that MaSep1 mediated the conidiation pattern shift by governing some genes associated with conidiation, cell division, and cell wall formation.

Integrated analysis of differently expressed microRNAs and mRNAs at different postnatal stages reveals intramuscular fat deposition regulation in goats (Capra hircus).

Intramuscular fat refers to the adipose tissue distributed in the muscle. It is an important indicator that affects the quality of goat meat, and can directly affect the tenderness and flavor of goat meat. Our previous study revealed the mRNA that may be crucial for intramuscular fat deposition during goat growth; however, how the microRNAs (miRNAs) are involved in the process is largely unclear. In the present study, a total of 401 known miRNAs and 120 goat novel miRNAs, including 110 differentially expressed (DE) miRNAs, were identified among longissimus dorsi from three growth stages (2, 9, and 24 months) by miRNA sequencing. Combining analysis of the DE mRNAs and DE miRNAs was then performed by miRDB and miRwalk, and miR-145-5p and FOXO1, miR-487b-3p, and PPARG coactivator 1 α (PPARGC1A), miR-345-3p, and solute carrier family 2 member 4 (SLC2A4), etc. were shown to closely associate with lipid metabolism, which was then validated by a correlation analysis. The final DE mRNAs were significantly enriched in fatty acid transmembrane transport, fatty acid homeostasis, apelin signaling pathway, glucagon signaling pathway, insulin signaling pathway, and AMPK signaling pathway by gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Besides, miR-145-5p showed a certain effect on goat intramuscular fat metabolism by acting on the possible target gene Forkhead Box O1 (FOXO1). These data provide some theoretical support for improving the quality of goat meat.

FOXD2 regulations IQGAP3 mediated Ca2+ signaling pathway to facilitate gastric adenocarcinoma cell promotion.

As a transcriptional factor, the Forkhead box (FOX) gene family is closely connected with apoptosis, proliferation, and other cellular processes. FOXD2, as one descendant of the FOX gene family, has been mentioned in many articles to show a high expression in several cancers. However, whether FOXD2 has a connection with gastric adenocarcinoma remains an unanswered question. Expression of FOXD2 and IQGAP3 in gastric adenocarcinoma was evaluated by bioinformatics analysis, which was further detected by real-time quantitative PCR (qRT-PCR) and western blot. The downstream target genes of FOXD2 were also mined by bioinformatics analysis. Pathway enrichment analysis was then performed on the target genes. Chromatin immunoprecipitation assay (ChIP) and dual-luciferase reporter assay were conducted to validate the regulatory relationship between FOXD2 and its downstream target gene IQGAP3. Methyl thiazolyl tetrazolium assay (MTT), combined with cell colony formation assay, was employed to assess the effect of FOXD2 and IQGAP3 on the proliferation of gastric adenocarcinoma cells. Intracytoplasmic Ca2+ concentration was measured by Fluo-3 fluorescence staining. FOXD2 showed a high expression in gastric adenocarcinoma tissues and cells, and FOXD2 silencing considerably attenuated gastric adenocarcinoma cell proliferation. IQGAP3, a downstream target gene of FOXD2, had a positive connection with the expression of FOXD2. The binding relationship between FOXD2 and the promoter region of IQGAP3 was further verified by ChIP and dual-luciferase reporter assays. The results of cell function experiments indicated that FOXD2 could promote gastric adenocarcinoma cell proliferation by transcriptionally activating IQGAP3 to induce an increase in intracellular Ca2+ level. This study confirmed that FOXD2 increased intracellular Ca2+ level through transcriptional activation of IQGAP3, which in turn propelled the proliferation of gastric adenocarcinoma cells, revealing the considerable significance of FOXD2 in the development of gastric adenocarcinoma.

Regulation and Function of FOXC1 in Osteoblasts.

Estrogens, which bind to estrogen receptor alpha (ERα), are important for proper bone mineral density. When women go through menopause, estrogen levels decrease, and there is a decrease in bone quality, along with an increased risk for fractures. We previously identified an enhancer near FOXC1 as the most significantly enriched binding site for estrogen receptor alpha (ERα) in osteoblasts. FOXC1 is a transcription factor belonging to a large group of proteins known as forkhead box genes and is an important regulator of bone formation. Here, we demonstrate that 17β-estradiol (E2) increases the mRNA and protein levels of FOXC1 in primary mouse and human osteoblasts. GATA4 is a pioneer factor for ERα and it is also recruited to enhancers near Foxc1. Knockdown of Gata4 in mouse osteoblasts in vitro decreases Foxc1 expression as does knockout of Gata4 in vivo. Functionally, GATA4 and FOXC1 interact and regulate osteoblast proteins such as RUNX2, as demonstrated by ChIP-reChIP and luciferase assays. The most enriched motif in GATA4 binding sites from ChIP-seq is for FOXC1, supporting the notion that GATA4 and FOXC1 cooperate in regulating osteoblast differentiation. Together, these data demonstrate the interactions of the transcription factors ERα, GATA4, and FOXC1 to regulate each other's expression and other osteoblast differentiation genes.

Dysregulated Forkhead Box (FOX) Genes Association with Survival Prognosis, Anti-tumor Immunity, and Key Targeting Drugs in Colon Adenocarcinoma.

Several studies have revealed that the aberrant expressions of forkhead box (FOX) genes are associated with carcinogenesis. However, the crucial biological functions of the FOX gene in colon adenocarcinoma (COAD) remain unknown. The TCGA-COAD dataset (n=328) was utilized for determining the deregulated FOX genes and their association with functional enrichment, protein-protein interaction (PPI), survival prognosis, anti-tumor immunity, cancer-associated pathways, and biological processes in COAD. In addition, we used GSE166427 (GPL13667) as a validation cohort (n=196). Molecular docking studies were applied to perform the drug interactions. The FOX genes are deregulated in the COAD (Log2 FC>0.50, P<0.05), and the PPI network of FOX members is substantially related to the enrichment of cancerous signaling, immune responses, and cellular development (FDR<0.05). A worse prognosis for overall survival in COAD individuals is connected with the subgroup of FOX transcripts (P≤0.05). FOXD4, FOXH1, and FOXS1 were identified as predictive variables in the univariate and multivariate Cox regression models (P≤0.05). FOXH1 and FOXS1 are substantially linked to the deregulated immunity in COAD (R>0.20, P<0.01). Furthermore, FOXS1 expression regulates cancer-associated pathways and biological processes (P<0.05). Moreover, FOXD4, FOXH1, and FOXS1 are genetically altered and showed diagnostic efficacy in COAD. We revealed that FOXD4, FOXH1, and FOXS1 are consistently deregulated in GSE166427 (P<0.05). Finally, molecular docking revealed that FOXH1 interacted with various drugs, including belinostat, entinostat, and panobinostat. The FOX genes have a strong correlation with the poor prognosis for survival, tumor immunity, cancer-associated pathways, and biochemical processes that cause the pathogenesis of COAD.

Prospective clinical sequencing of 1016 Chinese prostate cancer patients: uncovering genomic characterization and race disparity.

Although there is a well-known disparity in prostate cancer (PC) incidence and mortality between Chinese and Western patients, the underlying genomic differences have been investigated only sparsely. This clinicogenomic study was conducted to reveal the genomic mutations contributing to the PC disparity across ethnicities and investigate the mutational profile of Chinese PC patients. A total of 1016 Chinese PC patients were prospectively enrolled and subjected to targeted sequencing, resulting in usable sequencing data for 41 genes from 859 patients. Genomic data retrieved from The Cancer Genome Atlas (TCGA; locoregional PC), Memorial Sloan Kettering Cancer Center [MSKCC; metastatic castration-sensitive PC (mCSPC)], and Stand Up To Cancer [SU2C; metastatic castration-resistant PC (mCRPC)] cohorts were used as comparators representing Western men. Genomic mutations were analyzed using an integrated bioinformatic strategy. A comparison of the disease stages revealed that mutations in tumor protein 53 (TP53), androgen receptor (AR), forkhead box A1 (FOXA1), and genes involved in the cell cycle pathway were enriched in mCRPC. Mutations in adenomatous polyposis coli (APC) gene were found to be more prevalent in patients with visceral metastasis. Genomic differences between Western and Chinese men were mainly observed in castration-sensitive PC, with tumors from Chinese men having more FOXA1 (11.4% vs. 4.2%) but fewer TP53 (4.8% vs. 13%) mutations in locoregional PC and harboring fewer TP53 (11% vs. 29.2%), phosphatase and tensin homolog (PTEN; 2.5% vs. 10.3%), and APC (1.7% vs. 7.4%) mutations in the mCSPC stage than those of Western men. Patients of both ethnicities with mCRPC had similar mutational spectra. Furthermore, FOXA1 class-2 was less common than FOXA1 class-1 and showed no enrichment in metastasis, contrary to the findings in the Western cohort. Our study provides a valuable resource for a better understanding of PC in China and reveals the genomic alterations associated with PC disparity across races.

Role of Fork-Head Box Genes in Breast Cancer: From Drug Resistance to Therapeutic Targets.

Breast cancer has been acknowledged as one of the most notorious cancers, responsible for millions of deaths around the globe. Understanding the various factors, genetic mutations, comprehensive pathways, etc., that are involved in the development of breast cancer and how these affect the development of the disease is very important for improving and revitalizing the treatment of this global health issue. The forkhead-box gene family, comprising 19 subfamilies, is known to have a significant impact on the growth and progression of this cancer. The article looks into the various forkhead genes and how they play a role in different types of cancer. It also covers their impact on cancer drug resistance, interaction with microRNAs, explores their potential as targets for drug therapies, and their association with stem cells.

Pan-cancer analyses reveal multi-omic signatures and clinical implementations of the forkhead-box gene family.

Forkhead box (FOX) proteins belong to one of the largest transcription factor families and play crucial roles in the initiation and progression of cancer. Prior research has linked several FOX genes, such as FOXA1 and FOXM1, to the crucial process of carcinogenesis. However, the overall picture of FOX gene family across human cancers is far from clear. To investigate the broad molecular signatures of the FOX gene family, we conducted study on multi-omics data (including genomics, epigenomics and transcriptomics) from over 11,000 patients with 33 different types of human cancers. Pan-cancer analysis reveals that FOX gene mutations were found in 17.4% of tumor patients with a substantial cancer type-dependent pattern. Additionally, high expression heterogeneity of FOX genes across cancer types was discovered, which can be partially attributed to the genomic or epigenomic alteration. Co-expression network analysis reveals that FOX genes may exert functions by regulating the expression of both their own and target genes. For a clinical standpoint, we provided 103 FOX gene-drug target-drug predictions and found FOX gene expression have potential survival predictive value. All of the results have been included in the FOX2Cancer database, which is freely accessible at http://hainmu-biobigdata.com/FOX2Cancer. Our findings may provide a better understanding of roles FOX genes played in the development of tumors, and help to offer new avenues for uncovering tumorigenesis and unprecedented therapeutic targets.

Variant Analysis of FOXE1 Gene in Non-Syndromic Cleft Lip and Palate Patients of Peshawar, Pakistan

One of the most common structural birth defects is the cleft lip and palate, having an incidence rate of 1:700 live births worldwide. It can be isolated cleft lip, isolated cleft palate or a combination of both cleft lip and palate. The orofacial cleft can be caused by a variety of genetic and environmental factors or through an interaction between these factors. The gene Fork-head Box protein E1 (FOXE1) has been documented to be involved with cleft lip and palate. The present study aims to screen mutations in FOXE1 and to correlate phenotype and genotype of affected individuals. After obtaining ethical approval, peripheral blood samples were collected from 100 affected individuals, irrespective of age and gender. The genomic DNA was extracted, followed by quality control through spectrophotometer and gel electrophoresis. Polymerase chain reaction (PCR) was carried out to perform the targeted Sanger sequencing of FOXE1 gene. A point mutation (c.274C&gt;T, rs3021526) in FOXE1 gene was detected in 15 samples. Based on phenotype, males and isolated cleft palate type was commonly involved,with bilateral occurrence, and moderate cases were frequently seen among the enrolled patients. In this study, a missense substitution was observed in gene FOXE1. This study provides a foundation for genetic counseling for families at risk and offer valuable insights for prevention and management plans.

Sevoflurane protects against intracerebral hemorrhage via microRNA-133b/FOXO4/BCL2 axis.

The application of Sevoflurane (Sev) in neurological diseases has been documented. We herein clarified the role of Sev in intracerebral hemorrhage (ICH). Through bioinformatics analysis, ICH-related microRNA (miRNA) was collected with microRNA-133b (miR-133b) chosen for the study subject. Then, the related downstream gene Forkhead box O4 (FOXO4) was identified. For in vivo assays, an ICH mouse model was established by autologous blood injection. For in vitro assays, hippocampal neurons were extracted from mouse brain tissues, and erythrocyte lysates were employed to simulate in vitro hemorrhage. Interaction between miR-133b and FOXO4 as well as between FOXO4 and BCL2 were assayed. We found decreased miR-133b in the brain tissue of ICH mice and erythrocyte lysate-treated hippocampal neurons. Sev treatment attenuated ICH and hippocampal neuronal apoptosis in mice by upregulating miR-133b. miR-133b targeted FOXO4 expression, and inhibition of FOXO4 attenuated hippocampal neuronal apoptosis by increasing BCL2 expression. Sev attenuated ICH in mice by increasing BCL2 expression through regulation of miR-133b-mediated FOXO4 expression. The findings highlighted the protective effect of Sev on ICH mice through the regulation of miR-133b-mediated FOXO4 expression.

An Integrated Study on the Differential Expression of the FOX Gene Family in Cancer and Their Response to Chemotherapy Drugs.

The Forkhead-box (FOX) transcription factors, as one of the largest gene families in humans, play key roles in cancer. Although studies have suggested that several FOX transcription factors have a significant impact on cancer, the functions of most of the FOX genes in cancer remain elusive. In the study, the expression of 43 FOX genes in 63 kinds of cancer diseases (including many subtypes of same cancer) and in response to 60 chemical substances was obtained from the Gene Expression Atlas database of the European Bioinformatics Institute. Based on the high degree of overlap in FOXO family members differentially expressed in various cancers and their particular responses to chemotherapeutic drugs, our data disclosed the FOX genes that played an important role in the development and progression of cancer. More importantly, we predicted the role of one or several combinatorial FOX genes in the diagnosis and prognostic assessment of a specific cancer and evaluated the potential of a certain anticancer drug therapy for this type of cancer by integrating patterns of FOX genes expression with anticancer drugs sensitivity.

Hsa_circ_0030042 Facilitates the Proliferation and Migration of Vascular Smooth Muscle Cells via the miR-514a-3p/FOXO1 Axis

Purpose: Circular RNA (circRNA) has been proved to play a vital role in atherosclerosis (AS) progression, and vascular smooth muscle cells (VSMCs) are involved in the progression of AS. However, the in-depth mechanism by which circRNA regulates VSMC proliferation and migration remains to be elusive. Methods: We used tumor necrosis factor-alpha (TNF-α) to treat VSMCs to establish a cell model of AS. We used Cell Counting Kit-8, terminal-deoxynucleoitidyl transferase–mediated nick end labeling, and transwell assays to assess the proliferation, apoptosis, and migration in TNF-α-induced VSMCs. Moreover, the interaction between molecules was measured by RNA-binding protein immunoprecipitation, RNA pull-down, and luciferase reporter assays. Results: Our study found that a novel circRNA hsa_circ_0030042, which is derived from its host gene forkhead box O1 (FOXO1), was upregulated in TNF-α-induced VSMCs. Silencing of hsa_circ_0030042 inhibited proliferation and migration while promoting apoptosis in TNF-α-induced VSMCs. Mechanically, hsa_circ_0030042 positively regulated FOXO1 expression via sponging miR-514a-3p. Conclusions: Our study stated the vital role of the hsa_circ_0030042/miR-514a-3p/FOXO1 axis and provides a profound understanding about the circRNA in AS.

FoxK1 is Required for Ectodermal Cell Differentiation During Planarian Regeneration.

Forkhead box (Fox) genes belong to the “winged helix” transcription factor superfamily. The function of some Fox genes is well known, such as the role of foxO in controlling metabolism and longevity and foxA in controlling differentiation of endodermal tissues. However, the role of some Fox factors is not yet well characterized. Such is the case of FoxK genes, which are mainly studied in mammals and have been implicated in diverse processes including cell proliferation, tissue differentiation and carcinogenesis. Planarians are free-living flatworms, whose importance in biomedical research lies in their regeneration capacity. Planarians possess a wide population of pluripotent adult stem cells, called neoblasts, which allow them to regenerate any body part after injury. In a recent study, we identified three foxK paralogs in the genome of Schmidtea mediterranea. In this study, we demonstrate that foxK1 inhibition prevents regeneration of the ectodermal tissues, including the nervous system and the epidermis. These results correlate with foxK1 expression in neoblasts and in neural progenitors. Although the triggering of wound genes expression, polarity reestablishment and proliferation was not affected after foxK1 silencing, the apoptotic response was decreased. Altogether, these results suggest that foxK1 would be required for differentiation and maintenance of ectodermal tissues.

Loss of Foxd4 Impacts Neurulation and Cranial Neural Crest Specification During Early Head Development.

The specification of anterior head tissue in the late gastrulation mouse embryo relies on signaling cues from the visceral endoderm and anterior mesendoderm (AME). Genetic loss-of-function studies have pinpointed a critical requirement of LIM homeobox 1 (LHX1) transcription factor in these tissues for the formation of the embryonic head. Transcriptome analysis of embryos with gain-of-function LHX1 activity identified the forkhead box gene, Foxd4, as one downstream target of LHX1 in late-gastrulation E7.75 embryos. Our analysis of single-cell RNA-seq data show Foxd4 is co-expressed with Lhx1 and Foxa2 in the anterior midline tissue of E7.75 mouse embryos, and in the anterior neuroectoderm (ANE) at E8.25 alongside head organizer genes Otx2 and Hesx1. To study the role of Foxd4 during early development we used CRISPR-Cas9 gene editing in mouse embryonic stem cells (mESCs) to generate bi-allelic frameshift mutations in the coding sequence of Foxd4. In an in vitro model of the anterior neural tissues derived from Foxd4-loss of function (LOF) mESCs and extraembryonic endoderm cells, expression of head organizer genes as well as Zic1 and Zic2 was reduced, pointing to a need for FOXD4 in regulating early neuroectoderm development. Mid-gestation mouse chimeras harbouring Foxd4-LOF mESCs displayed craniofacial malformations and neural tube closure defects. Furthermore, our in vitro data showed a loss of FOXD4 impacts the expression of cranial neural crest markers Twist1 and Sox9. Our findings have demonstrated that FOXD4 is essential in the AME and later in the ANE for rostral neural tube closure and neural crest specification during head development.

Circular RNA ubiquitin-associated protein 2 enhances autophagy and promotes colorectal cancer progression and metastasis via miR-582-5p/FOXO1 signaling

Numerous circular RNAs (circRNAs) have been identified as vital regulators in various cancers. The newly reported circular RNA ubiquitin-associated protein 2 (circUBAP2) is a critical player in cell growth and metastasis in various types of cancers, although its role in colorectal cancer (CRC) has yet to be fully elucidated. We find that circUBAP2 is upregulated in CRC tissues and cell lines to induce autophagy both in vitro and in vivo. The effects of circUBAP2 on migration, invasion, and proliferation may be partially related to autophagy. Mechanistically, we uncover that circUBAP2 can directly interact with miR-582-5p and subsequently act as a microRNA sponge to regulate the expression of the miR-582-5p target gene forkhead box protein O1 (FOXO1) and downstream signaling molecules, which collectively advance the progression and metastasis of CRC. These results suggest that circUBAP2 acts as an oncogene via a novel circUBAP2/miR-582-5p/FOXO1 axis, providing a potential biomarker and therapeutic target for CRC management.

Seed oil of Brucea javanica induces apoptosis through the PI3K/Akt signaling pathway in acute lymphocytic leukemia Jurkat cells.

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3β was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.

Forkhead Box I1 in Breast Carcinoma as a Potent Prognostic Factor.

Forkhead box (FOX) proteins are family of transcriptional factors and regulate cell growth and differentiation as well as embryogenesis and longevity. Previous studies have demonstrated that several FOX members regulate growth or metastasis of breast carcinoma, but clinical significance of total FOX members remains unclear. We first examined associations between expression of 40 FOX genes and TNM status of 19 breast carcinoma using microarray data. Subsequently, we immunolocalized FOXI1 in 140 breast carcinomas and evaluated its clinicopathological significance. In the microarray analysis, we newly identified that gene expression of FOXI1 was most pronouncedly linked to metastasis of the breast carcinoma among the FOX members examined. However, clinicopathological significance of FOXI1 has not been examined in the breast carcinoma. FOXI1 immunoreactivity was positive in 44 out of 140 (31%) of breast carcinomas, and it was significantly associated with stage, lymph node metastasis and distant metastasis. The FOXI1 status was significantly associated with worse prognosis of the breast cancer patients, and it turned out to be an independent prognostic factor for both distant disease-free survival and breast cancer-specific survival. These findings suggest that FOXI1 plays important roles in the metastasis of breast carcinoma and immunohistochemical FOXI1 status is a potent prognostic factor.

Genome-Wide Identification, Comparison, and Expression Analysis of Transcription Factors in Ascidian Styela clava.

Tunicates include diverse species, as they are model animals for evolutionary developmental biology study. The embryonic development of tunicates is known to be extensively regulated by transcription factors (TFs). Styela clava, the globally distributed invasive tunicate, exhibits a strong capacity for environmental adaptation. However, the TFs were not systematically identified and analyzed. In this study, we reported 553 TFs categorized into 60 families from S. clava, based on the whole genome data. Comparison of TFs analysis among the tunicate species revealed that the gene number in the zinc finger superfamily displayed the most significant discrepancy, indicating this family was under the highly evolutionary selection and might be related to species differentiation and environmental adaptation. The greatest number of TFs was discovered in the Cys2His2-type zinc finger protein (zf-C2H2) family in S. clava. From the point of temporal view, more than half the TFs were expressed at the early embryonic stage. The expression correlation analysis revealed the existence of a transition for TFs expression from early embryogenesis to the later larval development in S. clava. Eight Hox genes were identified to be located on one chromosome, exhibiting different arrangement and expression patterns, compared to Ciona robusta (C. intestinalis type A). In addition, a total of 23 forkhead box (fox) genes were identified in S. clava, and their expression profiles referred to their potential roles in neurodevelopment and sensory organ development. Our data, thus, provides crucial clues to the potential functions of TFs in development and environmental adaptation in the leathery sea squirt.

Oscillating waves of Fox, Cyclin and CDK gene expression indicate unique spatiotemporal control of cell cycling during nervous system development in onychophorans

Forkhead box (Fox) genes code for a class of transcription factors with many different fundamental functions in animal development including cell cycle control. Other important factors of cell cycle control are Cyclins and Cyclin-dependent kinases (CDKs). Here we report on the oscillating expression of three Fox genes, FoxM, FoxN14 (jumeaux) and FoxN23 (Checkpoint suppressor like-1), Cyclins and CDKs in an onychophoran, a representative of a relatively small group of animals that are closely related to the arthropods. Expression of these genes is in the form of several waves that start as dot-like domains in the center of each segment and then transform into concentric rings that run towards the periphery of the segments.This oscillating gene expression, however, occurs exclusively along the anterior-posterior body axis in the tissue ventral to the base of the appendages, a region where the central nervous system and the enigmatic ventral and preventral organs of the onychophoran develop. We suggest that the oscillating gene expression and the resulting waves of expression we report are likely correlated with cell cycle control during the development of the onychophoran nervous system. This intriguing patterning appears to be unique for onychophorans as it is not found in any of the arthropods we also investigated in this study, and is likely correlated with the slow embryonic development of onychophorans compared to arthropods.

The regulatory roles and mechanisms of the transcription factor FOXF2 in human diseases.

Many studies have focused on the relationship between transcription factors and a variety of common pathological conditions, such as diabetes, stroke, and cancer. It has been found that abnormal transcription factor regulation can lead to aberrant expression of downstream genes, which contributes to the occurrence and development of many diseases. The forkhead box (FOX) transcription factor family is encoded by the FOX gene, which mediates gene transcription and follow-up functions during physiological and pathological processes. FOXF2, a member of the FOX transcription family, is expressed in various organs and tissues while maintaining their normal structural and functional development during the embryonic and adult stages. Multiple regulatory pathways that regulate FOXF2 may also be controlled by FOXF2. Abnormal FOXF2 expression induced by uncontrollable regulatory signals mediate the progression of human diseases by interfering with the cell cycle, proliferation, differentiation, invasion, and metastasis. FOXF2 manipulates downstream pathways and targets as both a pro-oncogenic and anti-oncogenic factor across different types of cancer, suggesting it may be a new potential clinical marker or therapeutic target for cancer. However, FOXF2’s biological functions and specific roles in cancer development remain unclear. In this study, we provide an overview of FOXF2’s structure, function, and regulatory mechanisms in the physiological and pathological conditions of human body. We also discussed the possible reasons why FOXF2 performs the opposite function in the same types of cancer.