Erratum: Variations in the Wnt/β-Catenin Pathway Key Genes as Predictors of Cervical Cancer Susceptibility [Corrigendum].
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PROVIDER: S-EPMC7457665 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Erratum: Variations in the Wnt/β-Catenin Pathway Key Genes as Predictors of Cervical Cancer Susceptibility [Corrigendum].
Pharmacogenomics and personalized medicine 20200824
[This corrects the article DOI: 10.2147/PGPM.S248548.]. ...[more]
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Project description:BackgroundCervical cancer is the fourth most common and fatal tumor among women worldwide. The Wnt/β-catenin signaling pathway was etiologically involved in the cervical cancer model. Herein, we aimed to investigate whether germline genetic variations within the Wnt/β-catenin pathway can be genetic risk factors of cervical cancer.Patients and methodsA total of 305 samples (147 patients, 158 controls) were included. Eight genetic variations located in APC (rs454886), GSK3β (rs3755557), CTNNB1 (rs11564475, rs1798802, rs3864004, rs2293303, and rs4135385), and TCF7L2 (rs7903146) were genotyped via Sanger sequencing. The χ 2 test and non-conditional logistic regression were used in the single-locus analysis. Gene-gene interactions and haplotype construction in case-control samples were performed by the GMDR method and Haploview software, respectively.ResultsThe frequency of CTNNB1 rs1798802 GA+AA genotype was significantly lower in cervical cancer patients adjusted for age (OR=0.626, 95% CI=0.398-0.984). The mutant alleles of rs3864004 (A) and rs2293303 (T) located in CTNNB1 showed 1.513 (1.038-2.207), and 1.654 (1.020-2.683) fold increased risk of cervical cancer, respectively. Haplotype analysis showed no association between haplotypes of the CTNNB1 gene and cervical cancer risk. No significant contribution of interactions among genes in the Wnt pathway was identified.ConclusionWe concluded that the genetic variants in the CTNNB1 gene might contribute to the development of cervical cancer.
| S-EPMC7247596 | biostudies-literature
Project description:[This corrects the article DOI: 10.1111/eva.13176.].
| S-EPMC9423089 | biostudies-literature
Project description:Excessive activation of the Wnt signalling pathway in the articular cartilage is demonstrated to be related to the onset and severity of osteoarthritis (OA). However, few studies have investigated the association between variants in Wnt-pathway-related genes and the risk of OA by searching Pubmed and EMBASE. Totally, 471 knee OA patients and 532 controls were recruited from three hospitals to evaluate the associations of five genetic variants (rs61735963, rs2908004, rs10795550, rs1799986 and rs1127379) with the risk of knee OA. These polymorphisms were genotyped through polymerase chain reaction and Sanger sequencing. Genetic risk scores (GRSs) were calculated to evaluate the combined effect of these genetic variants. No significant association was found between OA risk and polymorphisms (rs61735963, rs10795550 or rs1127379). However, WNT16 rs2908004 polymorphism was correlated with a decreased risk of OA, especially among females, smokers, non-drinkers and individuals with age < 60 years or BMI ≥ 25. This SNP was also associated with Kellgren-Lawrence grade and CRP. Similarly, LRP1 rs1799986 polymorphism decreased the risk of OA among males, smokers, drinkers and individuals with age < 60 years or BMI ≥ 25. TT genotype was more frequent in the group of VAS ≥ 6 versus VAS < 6. A low GRS was positively correlated with a decreased risk of OA. In addition, rs2908004 or rs1799986 polymorphism reduces the expression of WNT16 or LRP1. In conclusion, two SNPs (rs2908004 and rs1799986) are associated with the decreased risk of OA by regulating the Wnt pathway.
| S-EPMC6850928 | biostudies-literature
Project description:The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.
| S-EPMC10762490 | biostudies-literature
Project description:A significant burden is placed on the lives of females due to cervical cancer, which is currently the leading cause of cancer death among women. Preferentially expressed antigen in melanoma (PRAME) belongs to the CTA gene family and was found to be abnormally expressed among different types of cancers. Our previous research also indicated that PRAME was highly expressed in cervical cancer compared with normal tissues. However, the roles and detailed mechanisms of PRAME have not been explored in cervical cancer. In the present study, the expression of PRAME in cervical tissues and cells was detected by immunohistochemistry (IHC), qRT-PCR, and Western blotting. Additionally, CCK-8, BrdU, scratch, transwell, and flow cytometry assays were conducted to explore the function of PRAME in regulating the malignant biological behaviors of cervical cancer cells. Nude mice were used to confirm the role of PRAME in tumor growth in vivo. Furthermore, the Wnt inhibitor MSAB was used to verify the role of PRAME in regulating the Wnt/β-catenin pathway both in vitro and in vivo. The results of IHC, qRT-PCR, and Western blotting showed that PRAME was highly expressed in cervical cancer tissues and cells. PRAME knockdown attenuated cell growth, migration, and invasion; induced G0/G1 arrest; and increased cell apoptosis in C33A and SiHa cells through Wnt/β-catenin signaling regulation. However, the upregulation of PRAME exhibited the opposite effects accordingly, which could be partly reversed via MSAB treatment. The growth rate of xenograft tumors was enhanced when PRAME was overexpressed via Wnt/β-catenin signaling activation. Taken together, PRAME is associated with cervical cancer occurrence and progression mediated by Wnt/β-catenin signaling, suggesting that PRAME might be a factor in manipulating cervical carcinogenesis and a potential therapeutic target.
| S-EPMC10046627 | biostudies-literature
Project description:BackgroundStudies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long non-coding RNA (lncRNA), was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer. However, its effects on cervical cancer has been kept unknown up to now. The present study was aimed to investigate the relationship between lncRNA CASC11 and cervical cancer and further explore the mechanism of CASC11 effect on cervical cancer progression.MaterialsQuantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of CASC11 in cancerous and adjacent normal tissues of patients with cervical cancer as well as in cell lines. The proliferation, migration, invasion and apoptosis were assayed after transfecting the cell with si-CASC11 or pcDNA3.1-CASC11. TOP/FOP-Flash luciferase reporter assay and western blot were used to analysis the activation of Wnt/β-catenin signaling pathway. Si-CASC11-transfected HeLa cells were subcutaneously inoculated into male athymic (nude) mice to investigate the effect of CASC11 on the tumor formation.ResultsWe discovered that CASC11, the expression of which was positively associated with the tumor size and the FIGO staging and negatively related to the patients' survival rate, was up-regulated in the cervical cancer tissues and cell lines. Silencing CASC11 inhibited the proliferation, migration as well as invasion and promoted the cell apoptosis. Conversely, overexpression of CASC11 facilitated the cancer cell's proliferation, migration and invasion ability and suppressed the apoptosis. Further study showed that CASC11 promoted the migration and invasion of cervical cancer cells by activating Wnt/β-catenin signaling pathway and silencing CASC11 inhibited the tumor growth in vivo.ConclusionOur study demonstrated that CASC11 promoted the cervical cancer progression by activating Wnt/β-catenin signaling pathway for the first time, which provides a new target or a potential diagnostic biomarker of the treatment for cervical cancer.
| S-EPMC6599525 | biostudies-literature
Project description:BackgroundKIF18B was identified as a potential oncogene by analysis of The Cancer Genome Atlas database.Materials and methodsWe assessed KIF18B expression and explored its clinical significance in cervical cancer tissues. We have also evaluated the effects of KIF18B on cervical cancer cell proliferation, migration, and invasion both in vitro and in vivo.ResultsOur results show that KIF18B is overexpressed in cervical cancer tissues and is associated with a large primary tumor size, an advanced FIGO stage, and an advanced tumor grade. Knockdown of KIF18B induces cell cycle G1-phase arrest and inhibits the proliferation, migration, and invasion of cervical cancer cells, whereas its overexpression promotes proliferation, migration, and invasion in these cells. Moreover, silencing of KIF18B reduces expression of CyclinD1, β-catenin, C-myc, and p-GSK3β expression.ConclusionThese data suggest that KIF18B can serve as a novel oncogene that promotes the tumorigenicity of cervical cancer cells by activating Wnt/β-catenin signaling pathway.
| S-EPMC5880519 | biostudies-literature
Project description:BackgroundThe Wnt/β-catenin signaling pathway plays a key role in stem cell maintenance in the colorectum. Rare high-penetrance genetic mutations in components of this pathway result in familial colorectal cancer, yet the impact of common, germline variants remains unknown.MethodsWe assessed 172 variants in 26 genes from the Wnt/β-catenin pathway in 809 colorectal cancer cases and 814 healthy controls, followed by replication of the top findings in another 691 cases and 775 controls. In silico informatic tools were used to predict functional effects of variants.ResultsEighteen SNPs in the pathway were significantly associated with colorectal cancer risk (P < 0.05) in the discovery phase. We observed a significant dose-response increase in colorectal cancer risk by number of risk genotypes carried (P = 4.19 × 10(-8)). Gene-based analysis implicated CSNK1D (P = 0.014), FZD3 (P = 0.023), and APC (P = 0.027) as significant for colorectal cancer risk. In the replication phase, FZD3:rs11775139 remained significantly associated with reduced risk with a pooled OR of 0.85 [95% confidence interval (CI), 0.76-0.94, P = 0.001]. Although borderline significant in the replication population, APC:rs2545162 was highly significant in the pooled analysis-OR, 1.42; 95% CI, 1.16-1.74; P = 0.00085. Functional assessment identified several potential biologic mechanisms underlying these associations.ConclusionsOur findings suggest that common germline variants in the Wnt/β-catenin pathway may be involved in colorectal cancer development.ImpactThese variants may be informative in colorectal cancer risk assessment to identify individuals at increased risk who would be candidates for screening.
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Project description:The bioflavonoid apigenin has been shown to possess cancer-preventive and anti-cancer activities. In a drug screening, we found that apigenin can inhibit Wnt/β-catenin signaling, a pathway that participates in pivotal biological functions, which dis-regulation results in various human diseases including cancers. However, the underlying mechanism of apigenin in this pathway and its link to anti-cancer activities remain largely unknown. Here we showed that apigenin reduced the amount of total, cytoplasmic, and nuclear β-catenin, leading to the suppression in the β-catenin/TCF-mediated transcriptional activity, the expression of Wnt target genes, and cell proliferation of Wnt-stimulated P19 cells and Wnt-driven colorectal cancer cells. Western blotting and immunofluorescent staining analyses further revealed that apigenin could induce autophagy-mediated down-regulation of β-catenin in treated cells. Treatment with autophagy inhibitors wortmannin and chloroquine compromised this effect, substantiating the involvement of autophagy-lysosomal system on the degradation of β-catenin during Wnt signaling through inhibition of the AKT/mTOR signaling pathway. Our data not only pointed out a route for the inhibition of canonical Wnt signaling through the induction of autophagy-lysosomal degradation of key player β-catenin, but also suggested that apigenin or other treatments which can initiate this degradation event are potentially used for the therapy of Wnt-related diseases including cancers.
| S-EPMC5428476 | biostudies-literature
Project description:Cervical cancer (CC) is the most prevalent gynecological malignancy occurring in the cervix. Long non-coding RNAs (lncRNAs) can act as oncogenes or anti-oncogenes in CC development. Here, we investigated the functional role and detailed mechanism of lncRNA pyruvate dehydrogenase E1 subunit beta antisense (PDHB-AS) in CC. At first, we found that PDHB-AS was significantly down-regulated in CC cells. Besides, overexpression of PDHB-AS repressed CC cell malignant behaviors. HKF-derived exosomes carried miR-4536-5p to CC cells and thereby inhibited PDHB-AS expression. Moreover, PDHB-AS inactivated the Wnt/β-catenin pathway via impeding the nuclear translocation of β-catenin in CC cells. In addition, miR-582-5p could bind with both PDHB-AS and Dickkopf-1 (DKK1). PDHB-AS recruited poly(A) binding protein cytoplasmic 1 (PABPC1) to inhibit Wnt7b expression. PDHB-AS interacted with RNA-binding motif protein X-linked (RBMX) to regulate cisplatin resistance in CC. Finally, we conducted in vivo experiments to confirm that HKF promoted CC tumor growth whereas PDHB-AS suppressed CC tumor growth. Collectively, PDHB-AS plays a tumor-suppressive role in the progression of CC, which suggests the therapeutic potential of PDHB-AS for CC.
| S-EPMC9905568 | biostudies-literature