FOXQ1 Expression Research Articles

Resveratrol triggers autophagy-related apoptosis to inhibit the progression of colorectal cancer via inhibition of FOXQ1.

Colorectal cancer (CRC) is a significant health problem with elevated mortality rates, prompting intense exploration of its complex molecular mechanisms and innovative therapeutic avenues. Resveratrol (RSV), recognised for its anticancer effects through SIRT1 activation, is a promising candidate for CRC treatment. This study focuses on elucidating RSV's role in CRC progression, particularly its effect on autophagy-related apoptosis. Using bioinformatics, protein imprinting and immunohistochemistry, we established a direct correlation between FOXQ1 and adverse CRC prognosis. Comprehensive in vitro experiments confirmed RSV's ability to promote autophagy-related apoptosis in CRC cells. Plasmids for SIRT1 modulation were used to investigate underlying mechanisms. Molecular docking, glutathione-S-transferase pull-down experiments and immunoprecipitation highlighted RSV's direct activation of SIRT1, resulting in the inhibition of FOXQ1 expression. Downstream interventions identified ATG16L as a crucial autophagic target. In vivo and in vitro studies validated RSV's potential for CRC therapy through the SIRT1/FOXQ1/ATG16L pathway. This study establishes RSV's capacity to enhance autophagy-related cell apoptosis in CRC, positioning RSV as a prospective therapeutic agent for CRC within the SIRT1/FOXQ1/ATG16L pathway.

Foxq1 Promotes Alveolar Epithelial Cell Death through Tle1-mediated Inhibition of the NFκB Signaling Pathway.

Acute lung injury is a common respiratory disease characterized by diffuse alveolar injury and interstitial edema, as well as a hyperinflammatory response, lung cell damage and oxidative stress. Foxq1, a member of the FOX family of transcription factors, is expressed in various tissues, such as the lungs, liver, and kidneys, and contributes to various biological processes, such as stress, metabolism, cell cycle arrest, and aging-related apoptosis. However, the role of Foxq1 in acute lung injury is unknown. We constructed ex vivo and in vivo acute lung injury models by lipopolysaccharide tracheal perfusion of ICR mice and conditioned medium stimulation of injured MLE-12 cells. Foxq1 expression was increased, and its localization was altered in our acute lung injury model. In normal or injured MLE-12 cells, knockdown of Foxq1 promoted cell survival, and overexpression had the opposite effect. This regulatory effect was likely mediated by Tle1 and the NFκB/Bcl2/Bax signaling pathway. These data suggest a potential link between Foxq1 and acute lung injury, indicating that Foxq1 can be used as a biomarker for the diagnosis of acute lung injury. Targeted inhibition of Foxq1 expression could promote alveolar epithelial cell survival and may provide a strategy for mitigating acute lung injury.

The tumor suppressor p53 is a negative regulator of the carcinoma-associated transcription factor FOXQ1

The forkhead box family transcription factor FOXQ1 is highly induced in several types of carcinomas, where it promotes epithelial-to-mesenchymal transition and tumor metastasis. The molecular mechanisms that lead to FOXQ1 deregulation in cancer are incompletely understood. Here, we used CRISPR-Cas9-based genomic locus proteomics and promoter reporter constructs to discover transcriptional regulators of FOXQ1 and identified the tumor suppressor p53 as a negative regulator of FOXQ1 expression. Chromatin immunoprecipitation followed by quantitative PCR as well as complementary gain and loss-of-function assays in model cell lines indicated that p53 binds close to the transcription start site of the FOXQ1 promoter, and that it suppresses FOXQ1 expression in various cell types. Consistently, pharmacological activation of p53 using nutlin-3 or doxorubicin reduced FOXQ1 mRNA and protein levels in cancer cell lines harboring wildtype p53. Finally, we observed that p53 mutations are associated with increased FOXQ1 expression in human cancers. Altogether, these results suggest that loss of p53 function-a hallmark feature of many types of cancer-derepresses FOXQ1, which in turn promotes tumor progression.

Follicular fluid-derived exosomes rejuvenate ovarian aging through miR-320a-3p-mediated FOXQ1 inhibition

Abstract Ovarian aging is mainly characterized by a progressive decline in oocyte quantity and quality, which ultimately leads to female infertility. Various therapies have been established to cope with ovarian aging, among which exosome-based therapy is considered a promising strategy that can benefit ovarian functions via multiple pathways. Here, we isolated and characterized exosomes derived from ovarian follicular fluid and profiled the differential expression patterns of noncoding exosomal RNAs in young and aged women. Treatment with young mouse-derived exosomes efficiently rescued ovarian function in aged mice. The follicular fluid exosomes from young mice and miR-320-3p can also promote the proliferation of ovarian granulosa cells and improve mitochondrial function from old mice in vitro. The mechanism may be involve that exosomes transfer miR-320-3p to granulosa cells, and inhibit the expression of FOXQ1. Exosomes also can increase the number of primordial and growing follicles, and improve the developmental ability of oocytes in the old mice in vivo. And hnRNPA2B1 controls miR-320-3p entry into exosomes. This work provides insights into the antiaging potential of follicular fluid-derived exosomes and the underlying molecular mechanisms, which may facilitate prevention of ovarian aging and an improvement in female fertility.

FOXQ1 promotes pancreatic cancer cell proliferation, tumor stemness, invasion and metastasis through regulation of LDHA-mediated aerobic glycolysis

Pancreatic cancer (PC), a gastrointestinal tract malignant tumor, has a poor prognosis due to early metastasis and limited response to chemotherapy. Therefore, identifying novel therapeutic approaches for PC is critical. Epithelial–mesenchymal transition (EMT) is known as the vital progress in PC development, we constructed the EMT-related prognosis model to screen out that FOXQ1 probably involving in the EMT regulation. FOXQ1 has been linked to the malignant process in a number of cancers. However, its function in PC is unknown. In our work, the expression of FOXQ1 was elevated in PC tissues, and a high level of FOXQ1 in PC was linked to patients’ poor prognosis. FOXQ1 overexpression promoted aerobic glycolysis and enhanced PC cell proliferation, tumor stemness, invasion, and metastasis. Whereas, FOXQ1 silencing showed the reverse effect. Furthermore, mechanistic studies indicated that FOXQ1 promotes LDHA transcription, and thus modulates aerobic glycolysis to enhance PC cell proliferation, tumor stemness, invasion, and metastasis by increasing LDHA expression. Therefore, these novel data suggest that FOXQ1 may be a possible therapeutic target in PC.

LINC00543 promotes colorectal cancer metastasis by driving EMT and inducing the M2 polarization of tumor associated macrophages

BackgroundThe interaction between the tumor-microenvironment (TME) and the cancer cells has emerged as a key player in colorectal cancer (CRC) metastasis. A small proportion of CRC cells which undergo epithelial-mesenchymal transition (EMT) facilitate the reshaping of the TME by regulating various cellular ingredients.MethodsImmunohistochemical analysis, RNA immunoprecipitation (RIP), RNA Antisense Purification (RAP), dual luciferase assays were conducted to investigate the biological function and regulation of LINC00543 in CRC. A series in vitro and in vivo experiments were used to clarify the role of LINC00543 in CRC metastasis.ResultsHere we found that the long non-coding RNA LINC00543, was overexpressed in colorectal cancer tissues, which correlated with advanced TNM stage and poorer prognosis of CRC patients. The overexpression of LINC00543 promoted tumorigenesis and metastasis of CRC cells by enhancing EMT and remodeling the TME. Mechanistically, LINC00543 blocked the transport of pre-miR-506-3p across the nuclear-cytoplasmic transporter XPO5, thereby reducing the production of mature miR-506-3p, resulting in the increase in the expression of FOXQ1 and induction of EMT. In addition, upregulation of FOXQ1 induced the expression of CCL2 that accelerated the recruitment of macrophages and their M2 polarization.ConclusionsOur study showed that LINC00543 enhanced EMT of CRC cells through the pre-miR-506-3p/FOXQ1 axis. This resulted in the upregulation of CCL2, leading to macrophages recruitment and M2 polarization, and ultimately stimulating the progression of CRC.

Kaposi's Sarcoma-Associated Herpesvirus Immediate Early Proteins Trigger FOXQ1 Expression in Oral Epithelial Cells, Engaging in a Novel Lytic Cycle-Sustaining Positive Feedback Loop.

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus that can replicate in oral epithelial cells to promote viral transmission via saliva. To identify novel regulators of KSHV oral infection, we performed a transcriptome analysis of KSHV-infected primary human gingival epithelial (HGEP) cells, which identified the gene coding for the host transcription factor FOXQ1 as the top induced host gene. FOXQ1 is nearly undetectable in uninfected HGEP and telomerase-immortalized gingival keratinocytes (TIGK) cells but is highly expressed within hours of KSHV infection. We found that while the FOXQ1 promoter lacks activating histone acetylation marks in uninfected oral epithelial cells, these marks accumulate in the FOXQ1 promoter in infected cells, revealing a rapid epigenetic reprogramming event. To evaluate FOXQ1 function, we depleted FOXQ1 in KSHV-infected TIGK cells, which resulted in reduced accumulation of KSHV lytic proteins and viral DNA over the course of 4 days of infection, uncovering a novel lytic cycle-sustaining role of FOXQ1. A screen of KSHV lytic proteins demonstrated that the immediate early proteins ORF45 and replication and transcription activator (RTA) were both sufficient for FOXQ1 induction in oral epithelial cells, indicating active involvement of incoming and rapidly expressed factors in altering host gene expression. ORF45 is known to sustain extracellular signal-regulated kinase (ERK) p90 ribosomal s6 kinase (RSK) pathway activity to promote lytic infection. We found that an ORF45 mutant lacking RSK activation function failed to induce FOXQ1 in TIGK cells, revealing that ORF45 uses a shared mechanism to rapidly induce both host and viral genes to sustain lytic infection in oral epithelial cells. IMPORTANCE The oral cavity is a primary site of initial contact and entry for many viruses. Viral replication in the oral epithelium promotes viral shedding in saliva, allowing interpersonal transmission, as well as spread to other cell types, where chronic infection can be established. Understanding the regulation of KSHV infection in the oral epithelium would allow for the design of universal strategies to target the first stage of viral infection, thereby halting systemic viral pathogenesis. Overall, we uncover a novel positive feedback loop in which immediate early KSHV factors drive rapid host reprogramming of oral epithelial cells to sustain the lytic cycle in the oral cavity.

The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth.

FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. Inhibition of MEK or ERK1/2 activities, or knockout of ERK2 but not ERK1 suppressed the FGFR1 signaling-promoted FOXQ1 gene expression. Inhibition of ERK2 in ERK1 knockout cells blocked, while ectopic expression of FOXQ1 in ERK2 knockout cells rescued the FGFR1-signaling-promoted cell growth. Mechanistically, c-FOS, an early response transcription factor upregulated by the FGFR1-MEK-ERK2 pathway, bound to the FOXQ1 promoter to mediate the FGFR1 signaling-promoted FOXQ1 expression. These results indicate that the FGFR1-ERK2-c-FOS-FOXQ1 regulatory axis plays an essential role in the FGFR1 signaling-promoted BC growth. Targeting ERK2 and FOXQ1 should block BC growth caused by a deregulated FGFR1 signaling.

DDR2 coordinates EMT and metabolic reprogramming as a shared effector of FOXQ1 and SNAI1.

While multiple transcription factors (TFs) have been recognized to drive epithelial-mesenchymal transition (EMT) in cancer, their interdependence and context-dependent functions are poorly understood. In this study, we show that FOXQ1 and SNAI1 act as independent TFs within the EMT program with a shared ability to upregulate common EMT TFs without reciprocally impacting the expression of one another. Despite this independence, human mammary epithelial cells (HMLE) with ectopic expression of either FOXQ1 or SNAI1 share a common gene set that is enriched for a DDR2 coexpression signature. Further analysis identified DDR2 as the most upregulated receptor tyrosine kinase and a shared downstream effector of FOXQ1 and SNAI1 in triple-negative breast cancer (TNBC) cell lines. Alteration of DDR2 expression in either FOXQ1 or SNAI1 driven EMT models or in TNBC cells resulted in a profound change of cell motility without significantly impacting EMT marker expression, cell morphology, or the stem cell population. Lastly, we demonstrated that knockdown of DDR2 in the FOXQ1-driven EMT model and TNBC cell line significantly altered the global metabolic profile, including glutamine-glutamate and Aspartic acid recycling.

Monocarboxylate transporter 1 is a novel target for breast cancer stem like-cell inhibition by diallyl trisulfide.

Diallyl trisulfide (DATS) is a promising small molecule phytochemical that exhibits in vitro and in vivo activity in multiple preclinical solid tumor models including breast cancer, but the underlying mechanism is not fully understood. We have shown previously that forkhead box Q1 (FoxQ1) transcription factor is a novel target for breast cancer stem-like cells (bCSC) inhibition by DATS. Analysis of the breast TCGA (The Cancer Genome Atlas) data revealed that FoxQ1 expression was positively associated with that of SLC16A1/monocarboxylate transporter 1 (MCT1). Western blot analysis confirmed increased expression of MCT1 protein in SUM159 (basal-like) and MCF-7 cells (luminal-type) stably transfected to overexpress FoxQ1. Furthermore, FoxQ1 was recruited to the promoter of SLC16A1/MCT1. Treatment of SUM159 and MCF-7 cell lines with DATS resulted in suppression of MCT1 protein level that was accompanied by a decrease in intracellular and secreted levels of lactate. Overexpression or knockdown of MCT1 protein failed to alter DATS-mediated inhibition of colony formation or cell migration when compared to corresponding control cells. On the other hand, overexpression of MCT1 protein conferred partial but statistically significant protection against DATS-mediated inhibition of bCSC fraction (CD49fhigh /CD44high and aldehyde dehydrogenase 1 activity). The size of the mammospheres was relatively smaller in the DATS-treated group compared to control group. Inhibition of bCSC upon DATS treatment was augmented by knockdown of the MCT1 protein. In conclusion, the present study reveals that MCT1 is a novel target for bCSC inhibition by DATS treatment.

The Novel lncRNA RP9P Promotes Colorectal Cancer Progression by Modulating miR-133a-3p/FOXQ1 Axis.

BackgroundThe long non-coding RNA (lncRNA) RP9 pseudogene (RP9P) is a pseudogene-derived lncRNA that has never been reported in cancer, and its function underlying tumorigenesis in colorectal cancer (CRC) remains unknown.MethodsRP9P and miR-133a-3p were filtered through bioinformatics analysis. The level of RP9P, miR-133a-3p, and FOXQ1 in CRC cell lines was detected by real-time PCR. Cell Counting Kit-8 and flow cytometric analyses were used to detect cell proliferation and apoptosis, respectively. Interactions between RP9P, miR-133a-3p, and FOXQ1 were confirmed by a dual-luciferase reporter assay.ResultsRP9P was overexpressed in CRC compared to normal control tissues and cells. Knockdown of RP9P inhibited CRC cell viability. RP9P directly interacted with miR-133a-3p, and miR-133a-3p downregulation abrogated the tumor-suppressing effect of RP9P knockdown. miR-133a-3p directly targeted FOXQ, which was positively regulated by RP9P. RP9P knockdown decreased FOXQ1 expression levels in CRC cells by directly targeting miR-133a-3p via a sponge mechanism. In addition, in vivo experiments in a xenograft model revealed that downregulated RP9P expression inhibited CRC cell tumorigenesis.ConclusionRP9P promotes colorectal cancer progression by regulating the miR-133a-3p/FOXQ1 axis.

Tetrahydrocurcumin protects against nonalcoholic fatty liver disease by improving lipid metabolism and redox homeostasis

• Tetrahydrocurcumin (THC) improves glucose and lipid metabolism disorders in nonalcoholic fatty liver disease (NAFLD) in mice. • THC regulates the expression of oxidoreductase genes and lipid-metabolizing enzyme genes in the liver of NAFLD mice. • THC increases the antioxidant capacity and inhibits lipid deposition in HepG2 cells by activating the NRF2 signaling pathway. Nonalcoholic fatty liver disease (NAFLD) is the most common liver metabolic disease in the world. In this study we investigated the effect of tetrahydrocurcumin (THC), a potent antioxidant, on NAFLD. We found that THC significantly reduced the body weight, serum and liver lipids, serum malondialdehyde (MDA) and fasting blood glucose (FBG) of male NAFLD mice induced by feeding a high-fat diet (HFD) for 8 weeks. A RNA-seq analysis revealed that THC also affected the expression of many genes involved in lipid metabolism in the liver of NAFLD mice, including increasing the mRNA expression of CYP51 and FOXQ1 . Moreover, THC significantly reduced sodium oleate-induced lipid accumulation, activated the NRF2 pathway, and up-regulated the mRNA expression of FGF21 in HepG2 cells. Overall, our study showed that THC can improve the antioxidant capacity of liver, which suggests that dietary THC may be used to treat NAFLD.

LncRNA TUG1 promotes bladder cancer malignant behaviors by regulating the miR-320a/FOXQ1 axis

BackgroundGrowing evidence has showed long noncoding RNAs (lncRNAs) play critical roles in bladder cancer (BC) progression. LncRNA taurine upregulated gene 1 (TUG1) was involved in the development of human malignancies. However, the intrinsic and concrete molecular mechanisms of TUG1 in BC remain largely unknown. MethodsExpression patterns of TUG1, miR-320a and FOXQ1 in BC tissues and cell lines were measured using qRT-PCR and western blot, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. The capacity of cell migration and invasion was evaluated using wound healing and transwell assay. Tumor xenograft assay was performed to further validate the role of TUG1 in BC progression. Dual luciferase reporter assay and FISH analysis were employed to verify the TUG1/miR-320a/FOXQ1 regulatory network. ResultsTUG1 was significantly higher expression in BC specimens and cell lines. TUG1 knockdown suppressed BC cells malignant behaviors in vitro and inhibited tumor growth and metastasis in vivo, while TUG1 overexpression promoted BC cells malignant behaviors in vitro. However, the function of miR-320a was opposite to that of TUG1, and miR-320a inhibitor partially eliminated the inhibitory effect of TUG1 knockdown on the malignant behavior of BC cells. As a microRNA sponge, TUG1 actively elevated FOXQ1 expression to sponge miR-320a and subsequently promoted BC cells malignant phenotypes. ConclusionTUG1 may have great potential as therapeutic target for BC, since TUG1 silencing inhibited cell proliferation, migration and invasion in BC, while promoted cell apoptosis, by regulating the miR-320a/FOXQ1 axis.

Foxq1 promotes metastasis of nasopharyngeal carcinoma by inducing vasculogenic mimicry via the EGFR signaling pathway

In nasopharyngeal carcinoma (NPC), the treatment of tumor metastasis and recurrence is challenging and is associated with poor clinical efficacy. Vasculogenic mimicry (VM) is a new blood-supply model of malignant tumor that is closely related to tumors’ distant metastasis. Our previous study demonstrated that miR-124 could target Foxq1 to inhibit NPC metastasis. Whether Foxq1 affects metastasis through vasculogenic mimicry is worth consideration. In this study, we show that VM formation positively correlates with the expression of Foxq1, and EGFR, and the TNM stage in 114 NPC patient samples. Meanwhile, we show that VM-positive NPC patients have a poor prognosis. Furthermore, using in vitro and vivo approaches, we confirm that Foxq1 has a significant effect on NPC metastasis through promoting VM formation, which could be effectively inhibited by EGFR inhibitors (Nimotuzumab or Erlotinib). Also a synergistic efficacy of anti-EGFR and anti-VEGF drugs has been found in NPC inhibition. Mechanistically, the luciferase reporter gene and CHIP assays show that Foxq1 directly binds to the EGFR promoter region and regulates EGFR transcription. In conclusion, our results show that Foxq1 is regulated by miR-124 and that it promotes NPC metastasis by inducing VM via the EGFR signaling pathway. Overall, these results provide a new theoretical support and a novel target selection for anti-VM therapy in the treatment of nasopharyngeal carcinoma.

Cis-Repression of Foxq1 Expression Affects Foxf2-Mediated Gene Expression in Palate Development.

Disruption of FOXF2, encoding a member of the Forkhead family transcription factors, has been associated with cleft palate in humans and mice. FOXF2 is located in a conserved gene cluster containing FOXQ1, FOXF2, and FOXC1. We found that expression of Foxq1 is dramatically upregulated in the embryonic palatal mesenchyme in Foxf2–/– mouse embryos. We show here that the Foxf2 promoter-deletion mutation caused dramatically increased expression of the cis-linked Foxq1 allele but had little effect on the Foxq1 allele in trans. We analyzed effects of the Foxf2 mutation on the expression of other neighboring genes and compared those effects with the chromatin domain structure and recently identified enhancer-promoter associations as well as H3K27ac ChIP-seq data. We show that the Foxf2 mutation resulted in significantly increased expression of the Foxq1 and Exoc2 genes located in the same topologically associated domain with Foxf2 but not the expression of the Foxc1 and Gmds genes located in the adjacent chromatin domain. We inactivated the Foxq1 gene in mice homozygous for a Foxf2 conditional allele using CRISPR genome editing and generated (Foxf2/Foxq1)+/– mice with loss-of-function mutations in Foxf2 and Foxq1 in cis. Whereas the (Foxf2/Foxq1)–/– mice exhibited cleft palate at birth similar as in the Foxf2–/– mice, systematic expression analyses of a large number of Foxf2-dependent genes revealed that the (Foxf2/Foxq1)–/– embryos exhibited distinct effects on the domain-specific expression of several important genes, including Foxf1, Shox2, and Spon1, in the developing palatal shelves compared with Foxf2–/– embryos. These results identify a novel cis-regulatory effect of the Foxf2 mutation and demonstrate that cis-regulation of Foxq1 contributed to alterations in palatal gene expression in Foxf2–/– embryos. These results have important implications for interpretation of results and mechanisms from studies of promoter- or gene-deletion alleles. In addition, the unique mouse lines generated in this study provide a valuable resource for understanding the cross-regulation and combinatorial functions of the Foxf2 and Foxq1 genes in development and disease.

Novel mechanistic targets of forkhead box Q1 transcription factor in human breast cancer cells.

The transcription factor forkhead box Q1 (FoxQ1) is overexpressed in different solid tumors including breast cancer, but the mechanism underlying its oncogenic function is still not fully understood. In this study, we compared RNA-seq data from FoxQ1 overexpressing SUM159 cells with that of empty vector-transfected control cells to identify novel mechanistic targets of this transcription factor. Analysis of The Cancer Genome Atlas (TCGA) data set revealed significantly higher expression of FoxQ1 in black breast cancer patients compared with white women with this disease. In contrast, expression of FoxQ1 was comparable in ductal and lobular carcinomas in the breast cancer TCGA data set. Complementing our published findings in basal-like subtype, immunohistochemistry revealed upregulation of FoxQ1 protein in luminal-type human breast cancer tissue microarrays when compared with normal mammary tissues. Many previously reported transcriptional targets of FoxQ1 (eg, E-cadherin, N-cadherin, fibronectin 1, etc) were verified from the RNA-seq analysis. FoxQ1 overexpression resulted in the downregulation of genes associated with cell cycle checkpoints, M phase, and cellular response to stress/external stimuli as evidenced from the Reactome pathway analysis. Consequently, FoxQ1 overexpression resulted in mitotic arrest in basal-like SUM159 and human mammary epithelial cell line, but not in luminal-type MCF-7 cells. Finally, we show for the first time that FoxQ1 is a direct transcriptional regulator of interleukin (IL)-1α, IL-8, and vascular endothelial growth factor in breast cancer cells as evidenced by chromatin immunoprecipitation assay. In conclusion, the present study reports novel mechanistic targets of FoxQ1 in human breast cancer cells.

Postoperative 24-h Acute Sleep Deprivation Improves Learning and Memory Through Inhibition of Tau Phosphorylation in the Hippocampal Neurons of Splenectomized Rats.

PurposeAs tau pathology is involved in impaired postoperative learning and memory in rats, we attempted to identify the possible mechanisms by which tau pathology affects postoperative sleep deprivation.MethodsAdult male Sprague-Dawley rats were randomly assigned into six groups as follows: the Control group, Anaesthesia group, Surgery group, Sleep deprivation (SD) group: 24-h SD with the modified multiple platform method (MMPM), Anaesthesia and SD (ASD) group, and Surgery and SD (SSD) group. Tau396 and FOXQ1 protein expression levels in the hippocampal neurons of all groups were analysed. Changes following co-culture of hippocampal neurons with IL-6 were detected by flow cytometry.ResultsTwenty-four hours of acute SD decreased the error scores on postoperative day 5 in the ASD and SSD groups compared with the Anaesthesia and Surgery groups. Compared with the tau levels in the Control group, tau levels in the Anaesthesia and Surgery groups were increased, but SD decreased the expression of tau in the ASD and SSD groups. The expression levels of tau and FOXQ1 were inversely regulated. When hippocampal neurons were co-cultured with IL-6, the same changes were observed.ConclusionPostoperative 24-h acute SD improves learning and memory through inhibition of tau phosphorylation and increases IL-6-induced expression of FOXQ1 in the hippocampal neurons of splenectomized rats.

Liposomal clodronate combined with Cisplatin or Sorafenib inhibits hepatocellular carcinoma cell proliferation, migration and invasion by suppressing FOXQ1 expression

The purpose of this study was to investigate the effect of liposomal clodronate combined with Cisplatin or Sorafenib on the FOXQ1 expression and biological function of hepatocellular carcinoma cell lines. The expression of FOXQ1 was determined in normal hepatic cell line and hepatocellular carcinoma cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). HepG2 and MHCC97H cells were administered low, medium and high concentrations of cisplatin (3, 5 and 7 μg/ml) or Sorafenib (2, 7 and 20 μg/ml) in combination with liposomal clodronate (LC, 20μg/ml), and the expression of FOXQ1 in each group was determined. Cell migration, MTT and transwell assays were used to determine the effects of the treatments on biological functions of HepG2 and MHCC97H cells. qRT-PCR showed that the expression of FOXQ1 mRNA was higher in the four hepatocellular carcinoma cell lines than in normal cells, and the expression of FOXQ1 mRNA in HepG2 and MHCC97H cells were more dominant. All the tested doses of Cisplatin, but only high dose Sorafenib down-regulated the expression of FOXQ1. However, Sorafenib at low and medium concentrations had no significant effect on the expression of FOXQ1. When Cisplatin or Sorafenib was administered in combination with LC, the expression level of FOXQ1 was significantly reduced. Cell migration, MTT and transwell assays showed that proliferation, migration and invasion were inhibited when each drug was administered alone, but was stronger when the drugs were combined with liposomal clodronate.Liposomal clodronate combined with Cisplatin or Sorafenib down-regulates the expression of FOXQ1 in HepG2 and MHCC97H hepatoma cells, and inhibits their proliferation, migration and invasion.

Identification of Genes Related to Clinicopathological Characteristics and Prognosis of Patients with Colorectal Cancer.

The aim of this study was to identify genes with clinical significance in colorectal cancer (CRC). Gene expression profiles of 585 CRC tissues and 61 normal colorectal tissues from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to identify differentially expressed genes (DEGs) between CRC and normal colorectal tissues. DAVID and KOBAS tools were used to explore Gene Ontology (GO) and KEGG pathways enriched by DEGs, respectively. In addition, TCGA data sets were also used to identify prognostic factors and develop a prognostic prediction model for CRC. A total of 353 DEGs including 117 upregulated and 236 downregulated genes in CRC were identified based on GSE32323 data set. These DEGs were significantly enriched in the biological process related to the regulation of cell proliferation and 50 signaling pathways, such as "TGF-beta signaling pathway," "Wnt signaling pathway," and "Jak-STAT signaling pathway." GCG, ADH1B, SLC4A4, ZG16, and CLCA4 were the top five downregulated in CRC. FOXQ1, LGR5, CLDN1, KRT23, and DPEP1 were the top five upregulated in CRC. KRT23 expression could affect tumor stage and regional lymph node metastasis in CRC patients. FOXQ1 expression could affect tumor distant metastasis in CRC patients. Survival analysis indicated that SLC4A4 expression was associated with the prognosis of CRC patients. Prognostic prediction model developed based on age, tumor stage, and SLC4A4 expression exhibited an efficient performance in predicting 1-, 3-, and 5-year overall survival of CRC patients. In conclusion, the current study identified several genes and pathways related to CRC, which provided new insight in understanding molecular mechanism of tumorigenesis and development of CRC.

Long Non-coding RNA MALAT1 Inhibits Neuron Apoptosis and Neuroinflammation While Stimulates Neurite Outgrowth and Its Correlation With MiR-125b Mediates PTGS2, CDK5 and FOXQ1 in Alzheimer's Disease.

This study aimed to investigate the effect of long noncoding ribonucleic acids (RNAs) metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) on regulating neuron apoptosis, neurite outgrowth and inflammation, and further explore its molecule mechanism in Alzheimer's disease (AD). Control overexpression, lnc-MALAT1 overexpression, control shRNA, and lnc-MALAT1 shRNA were transfected into NGF-stimulated PC12 cellular AD model and cellular AD model from primary cerebral cortex neurons of rat embryo, which were established by Aβ1-42 insult. Rescue experiments were performed by transferring lnc-MALAT1 overexpression and lnc-MALAT1 overexpression & miR-125b overexpression plasmids. Neuron apoptosis, neurite outgrowth and inflammation were detected by Hoechst-PI/apoptosis marker expressions, and observations were made using microscope and RT-qPCR/Western blot assays. PTGS2, CDK5 and FOXQ1 expressions in rescue experiments were also determined. In two AD models, lnc-MALAT1 overexpression inhibited neuron apoptosis, promoted neurite outgrowth, reduced IL-6 and TNF-α levels, and increased IL-10 level compared to control overexpression, while lnc-MALAT1 knockdown promoted neuron apoptosis, repressed neurite outgrowth, elevated IL-6 and TNF-α levels, but reduced IL-10 level compared to control shRNA. Additionally, lnc- MALAT1 reversely regulated miR-125b expression, while miR-125b did not influence the lnc- MALAT1 expression. Subsequently, rescue experiments revealed that miR-125b induced neuron apoptosis, inhibited neurite outgrowth and promoted inflammation, also increased PTGS2 and CDK5 expressions but decreased FOXQ1 expression in lnc-MALAT1 overexpression treated AD models. Lnc-MALAT1 might interact with miR-125b to inhibit neuron apoptosis and inflammation while promote neurite outgrowth in AD.