Fzd10 wnt pathway

BACKGROUND: Chronic intestinal inflammatory diseases play a crucial role in the onset of colorectal cancer (CRC). Effectively impeding the progression of colitis-associated colorectal cancer (CAC) can be instrumental in hindering CRC development. Wu-Mei-Pill (WMP), a formulation comprising various herbal extracts, is clinically employed for CAC treatment, yet the underlying mechanism of WMP's efficacy in CAC remains unclear. Our study firstly demonstrated the effects and mechanisms of WMP on transcriptional and metabolic levels based on integrated transcriptomics and untargeted metabolomics and relative experimental validations...

Endometritis is one of the important reasons for the low fecundity of dairy cows, which has brought huge economic losses to the dairy industry. Emerging evidence suggests that miR-92b is a novel therapeutic molecule that plays a crucial role in many inflammatory diseases. However, its mechanism in lipoteichoic acid (LTA) induced endometritis remains unclear. In the present study, we explored the mechanism of miR-92b on LTA-induced endometritis in vivo and in vitro. The result displayed that the expression of miR-92b was reduced in LTA induced mouse endometritis and bovine endometrial epithelial cell lines (BEND)...

Sry-box9 (SOX9) maintains stem cell properties and plays crucial roles in many cancers. However, whether SOX9 is correlated with cervical cancer cell stemness and its detailed mechanism remains obscure. We studied the relationship between SOX9 and prognosis of cervical cancer through public database, and SOX9 was related to poor prognosis of cervical cancer. Elevated SOX9 expression enhanced the self-renewal properties and promotes tumorigenicity in cervical cancer. Overexpression of SOX9 could promote the expression of stem cell-related factors in cervical cancer cells and xenografts...

The p63 transcription factor is critical for epidermis formation in embryonic development, but its role in the adult epidermis is poorly understood. Here we show that acute genetic ablation of ΔNp63, the main p63 isoform, in adult epidermis disrupts keratinocyte proliferation and self-maintenance and, unexpectedly, triggers an inflammatory psoriasis-like condition. Mechanistically, single-cell RNA sequencing revealed down-regulation of cell cycle genes, up-regulation of differentiation markers, and induction of several pro-inflammatory pathways in ΔNp63-ablated keratinocytes...

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a deficiency of early diagnosis biomarkers and therapeutic targets. Drug resistance accounts for most HCC-related deaths, yet the mechanisms underlying drug resistance remain poorly understood. METHODS: Expression of Frizzled-10 (FZD10) in liver cancer stem cells (CSCs) was identified by means of RNA sequencing and validated by means of real-time polymerase chain reaction and immunohistochemistry...

Cashmere goat from Inner Mongolia is an excellent local breed in China, and the related cashmere product is a kind of precious textile raw material with high price. Cashmere is generated from secondary hair follicles, which has obvious annual periodicity and includes three different stages: anagen, catagen, and telogen. Therefore, we investigated skin transcriptome data for 12 months using weighted gene co-expression network analysis (WGCNA) to explore essential modules, pathways, and genes responsible for the periodic growth and development of secondary hair follicles...

Frizzled (FZD) proteins are primary receptors for Wnt signaling that activates the mitogen-activated protein kinase (MAPK) pathways. Dysfunction of Wnt signals with consequently abnormal activation of MAPK3 pathways was found in colorectal cancer (CRC) and gastric cancer (GC). Upregulation of FZD10 protein, localized in the exosomes isolated from plasma of CRC and GC patients, was associated with a poor prognosis. Herein, the expression levels of circulating FZD10 were found to be strongly correlated to their expression levels in the corresponding tissues in CRC and GC patients...

Exosomes belong to the family of extracellular vesicles released by every type of cell both in normal and pathological conditions. Growing interest in studies indicates that extracellular vesicles, in particular, the fraction named exosomes containing lipids, proteins and nucleic acid, represent an efficient way to transfer functional cargoes between cells, thus combining all the other cell-cell interaction mechanisms known so far. Only a few decades ago, the involvement of exosomes in the carcinogenesis in different tissues was discovered, and very recently it was also observed how they carry and modulate the presence of Wnt pathway proteins, involved in the carcinogenesis of gastrointestinal tissues, such as Frizzled 10 protein (FZD10), a membrane receptor for Wnt...

The aim of the present study was to investigate the role of miR-92a in lipid metabolism in hypoxic rats. Microarray analysis and reverse transcription-quantitative (RT-q)PCR were used to detect changes in the mRNA expression levels of miR-92a in the epididymal fat of hypoxic and normoxic rats. The downstream target mRNA of miR-92a was predicted using bioinformatics analysis and verified using a dual luciferase reporter assay. Changes in the expression of frizzled (Fzd)10 and c-Myc in the epididymal fat were detected using RT-qPCR and western blotting...

BACKGROUND: Nasopharyngeal carcinoma tends to present at an advanced stage because the primary anatomic site is located in a less visible area and its clinical symptoms are nonspecific. Prognosis of advanced nasopharyngeal carcinoma cases remains disappointing. SEPT9 is a methylation-based biomarker approved by the US Food and Drug Administration for colorectal cancer screening and diagnosis. Interestingly, downregulation of SEPT9, especially SEPT9_v2, mediated by promoter hypermethylation has been also detected in head and neck squamous cell carcinoma than in head and neck squamous epithelium, while other SEPT9 variants did not...

The objective of this study was to analyze the expression and clinical role of Wnt pathway molecules in metastatic high-grade serous carcinoma (HGSC). mRNA expression by qPCR of 20 molecules related to Wnt signaling (WNT1, WNT2, WNT3, WNT4, WNT5A, WNT6, WNT7, WNT11, FZD1, FZD4, FZD5, FZD6, FZD7, FZD8, FZD10, LRP5, LRP6, DKK, CCND, RUNX2) was analyzed in 87 HGSC effusions. Thirty-nine surgical specimens (19 ovarian, 20 from other intra-abdominal sites) were analyzed for comparative purposes. Protein expression of YAP and LRP and their phosphorylated forms by western blotting were analyzed in 52 tumors...

Extracellular vesicles (EVs) are involved in intercellular communication during carcinogenesis, and cancer cells are able to secrete EVs, in particular exosomes containing molecules, that can be transferred to recipient cells to induce pathological processes and significant modifications, as metastasis, increase of proliferation, and carcinogenesis evolution. FZD proteins, a family of receptors comprised in the Wnt signaling pathway, play an important role in carcinogenesis of the gastroenteric tract. Here, a still unknown role of Frizzled 10 (FZD10) protein was identified...

Colorectal adenomas are precursor lesions of colorectal adenocarcinoma. The transition from adenoma to carcinoma in patients with colorectal cancer (CRC) has been associated with an accumulation of genetic aberrations. However, criteria that can screen adenoma progression to adenocarcinoma are still lacking. This present study is the first attempt to identify genetic aberrations, such as the somatic mutations, copy number variations (CNVs), and high-frequency mutated genes, found in Thai patients. In this study, we identified the genomic abnormality of two sample groups...

This study aimed to identify specific microRNAs (miRNAs) related to postmenopausal osteoporosis (OP) in human. A total of 67 conserved miRNAs, including 50 miRNAs significantly up-regulated and 17 miRNAs significantly downregulated, showed differential expression between OP group and control group. 180 hairpin structures were predicted and 199 potential novel miRNA candidates with 18 to 25 nt in length, which will greatly enrich the human miRBase. 4 miRNAs (miR-518b, miR-582-3p, miR-148a-3p and miRNA-223-3p) had upregulated expression and 4 (miR-7d-5p, miR-210-3p, miR-324-5p and miR-654-3p) showed down-regulated expression...

Despite the high initial response rates to PARP inhibitors (PARPi) in BRCA -mutated epithelial ovarian cancers (EOC), PARPi resistance remains a major challenge. Chemical modifications of RNAs have emerged as a new layer of epigenetic gene regulation. N6 -methyladenosine (m6 A) is the most abundant chemical modification of mRNA, yet the role of m6 A modification in PARPi resistance has not previously been explored. Here, we show that m6 A modification of FZD10 mRNA contributes to PARPi resistance by upregulating the Wnt/β-catenin pathway in BRCA -mutated EOC cells...

The physis is a well-established and anatomically distinct cartilaginous structure that is crucial for normal long-bone development and growth. Abnormalities in physis function are linked to growth plate disorders and other pediatric musculoskeletal diseases. Understanding the molecular pathways operative in the physis may permit development of regenerative therapies to complement surgically-based procedures that are the current standard of care for growth plate disorders. Here, we performed next generation RNA sequencing on mRNA isolated from human physis and other skeletal tissues (e...

Acquired resistance to 5-fluorouracil (5-FU) frequently occurs in patients with hepatocellular carcinoma (HCC), the underlying molecular mechanisms of which are poorly understood. The aim of this study was to identify candidate genes and associated signalling pathways that may play a role in developing drug resistance following repeated 5-FU treatments. In this work, we established 5-FU-resistant cells (HepG2/5-FU) using stepwise increasing concentrations of 5-FU in parental HepG2 cells. Using transcriptome sequencing, we found that the expressions of the Wnt signalling genes, including negative regulators (DKK1, DKK3, ZNRF3, RNF43 and APC2) and positive regulators (FZD10 and DVL1), were significantly downregulated and upregulated in HepG2/5-FU cells, respectively, resulting in increased Wnt signalling...

Liver tumor-initiating cells (TICs), the drivers for liver tumorigenesis, accounts for liver tumor initiation, metastasis, drug resistance and relapse. Wnt/β-catenin signaling pathway emerges as a critical modulator in liver TIC self-renewal. However, the molecular mechanism of Wnt/β-catenin initiation in liver tumorigenesis and liver TICs is still elusive. Here, we examined the expression pattern of 10 Wnt receptors (FZD1-FZD10), and found only FZD6 is overexpressed along with liver tumorigenesis. What's more, a divergent lncRNA of FZD6, termed lncFZD6, is also highly expressed in liver cancer and liver TICs...

Leflunomide (LEF), an inhibitor of dihydroorotate dehydrogenase (DHODH) in pyrimidine biosynthetic pathway, is an immunomodulatory agent approved for the treatment of rheumatoid arthritis. In this study, we show that LEF significantly reduced cell proliferation of renal carcinoma cells in a concentration-dependent manner. LEF at 50 μM induced S-phase arrest and autophagy. Higher doses of LEF (>50 μM) effectively induced cell apoptosis. Modulating the concentration of LEF resulted in distinct effects on the expression of regulatory proteins associated with cell cycle, apoptosis, and autophagy...

The frog, Xenopus laevis, possesses a high capacity to regenerate various larval tissues, including the lens, which is capable of complete regeneration from the cornea epithelium. However, the molecular signaling mechanisms of cornea-lens regeneration are not fully understood. Previous work has implicated the involvement of the Wnt signaling pathway, but molecular studies have been very limited. Iris-derived lens regeneration in the newt (Wolffian lens regeneration) has shown a necessity for active Wnt signaling in order to regenerate a new lens...