scholarly journals FOXA1 can be modulated by HDAC3 in the progression of epithelial ovarian carcinoma

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Tong Lou ◽  
Chongdong Liu ◽  
Hong Qu ◽  
Zhiqiang Zhang ◽  
Shuzhen Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Malignant Tumors ◽  
Animal Experiments ◽  
Tumor Formation ◽  
Epithelial Ovarian Carcinoma ◽  
Expression Level ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells

AbstractFOXA1 is associated with malignant tumors, but the function of FOXA1 in EOC is unclear. HDAC3 can influence the proliferation, migration and invasion ability of EOC. In this study, we wanted to explore the function of FOXA1 in ovarian cancer and the relationship between HDAC3 and FOXA1.The expression of HDAC3 and FOXA1 was detected by immunohistochemical staining of primary lesions from 127 epithelial ovarian carcinoma patients. A proliferation assay, a Transwell assay, an apoptosis assay and animal experiments were used to assess the proliferation, invasion and apoptosis abilities of ovarian cancer cells before and after transfection with FOXA1. The relevance of the in vitro findings was confirmed in xenografts. The H-scores for FOXA1 and HDAC3 staining in FIGO stage III-IV were noticeably higher and predicted adverse clinical outcomes in patients with ovarian cancer. The expression level of HDAC3 was significantly correlated with the expression level of FOXA1. Invasion, proliferation and apoptosis capacity and tumor formation were decreased in the FOXA1-knockdown cells. Experiments in xenografts confirmed that HDAC3 mediated tumor formation. In conclusion, FOXA1 can be modulated by HDAC3 through the Wnt/β-catenin signaling pathway, and FOXA1 plays essential roles in the proliferation, apoptosis and invasion of EOC cell lines and xenograft experiments.

scholarly journals FOXA1 Can Be Modulated by HDAC3 in the Progression of Epithelial Ovarian Carcinoma

2021 ◽  
Author(s):  
Tong Lou ◽  
Chongdong Liu ◽  
Hong Qu ◽  
Zhiqiang Zhang ◽  
Shuzhen Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Malignant Tumors ◽  
Animal Experiments ◽  
Tumor Formation ◽  
Epithelial Ovarian Carcinoma ◽  
Expression Level ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells

Abstract FOXA1 is associated with malignant tumors, but the function of FOXA1 in EOC is unclear. HDAC3 can influence the proliferation, migration and invasion ability of EOC. In this study, we wanted to explore the function of FOXA1 in ovarian cancer and the relationship between HDAC3 and FOXA1.The expression of HDAC3 and FOXA1 was detected by immunohistochemical staining of primary lesions from 127 epithelial ovarian carcinoma patients. A proliferation assay, a Transwell assay, an apoptosis assay and animal experiments were used to assess the proliferation, invasion and apoptosis abilities of ovarian cancer cells before and after transfection with FOXA1. The relevance of the in vitro findings was confirmed in xenografts. The H-scores for FOXA1 and HDAC3 staining in FIGO stage III-IV were noticeably higher and predicted adverse clinical outcomes in patients with ovarian cancer. The expression level of HDAC3 was significantly correlated with the expression level of FOXA1. Invasion, proliferation and apoptosis capacity and tumor formation were decreased in the FOXA1-knockdown cells. Experiments in xenografts confirmed that HDAC3 mediated tumor formation. In conclusion, FOXA1 can be modulated by HDAC3 through the Wnt/β-catenin signaling pathway, and FOXA1 plays essential roles in the proliferation, apoptosis and invasion of EOC cell lines and xenograft experiments.

scholarly journals Splicing factor USP39 promotes ovarian cancer malignancy through maintaining efficient splicing of oncogenic HMGA2

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Shourong Wang ◽  
Zixiang Wang ◽  
Jieyin Li ◽  
Junchao Qin ◽  
Jianping Song ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Malignant Tumors ◽  
Splicing Factor ◽  
Ovarian Cancer Cells ◽  
Nuclear Speckles ◽  
Aberrant Expression ◽  
Intergenic Regions

AbstractAberrant expression of splicing factors was found to promote tumorigenesis and the development of human malignant tumors. Nevertheless, the underlying mechanisms and functional relevance remain elusive. We here show that USP39, a component of the spliceosome, is frequently overexpressed in high-grade serous ovarian carcinoma (HGSOC) and that an elevated level of USP39 is associated with a poor prognosis. USP39 promotes proliferation/invasion in vitro and tumor growth in vivo. Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells. We further demonstrated that USP39 colocalizes with spliceosome components in nuclear speckles. Transcriptomic analysis revealed that USP39 deletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions. Furthermore, RNA immunoprecipitation sequencing showed that USP39 preferentially binds to exon-intron regions near 5′ and 3′ splicing sites. In particular, USP39 facilitates efficient splicing of HMGA2 and thereby increases the malignancy of ovarian cancer cells. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor in ovarian cancer and represents a potential target for ovarian cancer therapy.

scholarly journals Tripartite Motif 16 Inhibits the Migration and Invasion in Ovarian Cancer Cells

2017 ◽  
Vol 25 (4) ◽  
pp. 551-558 ◽  
Author(s):  
Hongwei Tan ◽  
Jin Qi ◽  
Guanghua Chu ◽  
Zhaoyang Liu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Hedgehog Signaling ◽  
Epithelial Mesenchymal Transition ◽  
Coiled Coil ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Tripartite Motif

Tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite motif (TRIM) protein family, has been shown to play a role in tumor development and progression. However, the role of TRIM16 in ovarian cancer has never been revealed. Thus, in this study, we investigated the roles and mechanisms of TRIM16 in ovarian cancer. Our results demonstrated that TRIM16 expression was low in ovarian cancer cell lines. In addition, overexpression of TRIM16 significantly inhibited the migration and invasion in vitro, as well as suppressed the epithelial‐mesenchymal transition (EMT) phenotype in ovarian cancer cells. Furthermore, overexpression of TRIM16 greatly inhibited the protein expression levels of Shh, Smo, Ptc, Gli-1, MMP2, and MMP9 in ovarian cancer cells. Taken together, these results strongly suggest that TRIM16 inhibits the migration and invasion via suppressing the Sonic hedgehog signaling pathway in ovarian cancer cells. Thus, TRIM16 may be a novel potential therapeutic target for ovarian cancer.

scholarly journals The polypeptide GALNT6 Displays Redundant Functions upon Suppression of its Closest Homolog GALNT3 in Mediating Aberrant O-Glycosylation, Associated with Ovarian Cancer Progression

2019 ◽  
Vol 20 (9) ◽  
pp. 2264 ◽  
Author(s):  
Razan Sheta ◽  
Magdalena Bachvarova ◽  
Elizabeth Macdonald ◽  
Stephane Gobeil ◽  
Barbara Vanderhyden ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Functional Redundancy ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Gene Ablation

Epithelial ovarian cancer (EOC) represents the most lethal gynecologic malignancy; a better understanding of the molecular mechanisms associated with EOC etiology could substantially improve EOC management. Aberrant O-glycosylation in cancer is attributed to alteration of N-acetylgalactosaminyltransferases (GalNAc-Ts). Reports suggest a genetic and functional redundancy between GalNAc-Ts, and our previous data are indicative of an induction of GALNT6 expression upon GALNT3 suppression in EOC cells. We performed single GALNT3 and double GALNT3/T6 suppression in EOC cells, using a combination of the CRISPR-Cas9 system and shRNA-mediated gene silencing. The effect of single GALNT3 and double GALNT3/T6 inhibition was monitored both in vitro (on EOC cells roliferation, migration, and invasion) and in vivo (on tumor formation and survival of experimental animals). We confirmed that GALNT3 gene ablation leads to strong and rather compensatory GALNT6 upregulation in EOC cells. Moreover, double GALNT3/T6 suppression was significantly associated with stronger inhibitory effects on EOC cell proliferation, migration, and invasion, and accordingly displayed a significant increase in animal survival rates compared with GALNT3-ablated and control (Ctrl) EOC cells. Our data suggest a possible functional redundancy of GalNAc-Ts (GALNT3 and T6) in EOC, with the perspective of using both these enzymes as novel EOC biomarkers and/or therapeutic targets.

Critical role of SEMA5A expression in invasion and metastasis of ovarian cancer cell

2014 ◽  
Vol 2 (4) ◽  
pp. 247-259
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Critical Role ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Cancer Tissue ◽  
Invasion And Metastasis

Semaphorins are a large family of genes involved in the development and morphogenesis of the nervous system. SEMA5A has been reported as a bi-functional molecule, acting as both oncogene and tumor suppressor in different types of cancer. High expression levels of SEMA5A and its receptor, Plexin-B3, were associated with aggressiveness in pancreatic and prostate cancers. Our previous study in ovarian cancer metastasis indicates that FAK knock-down can suppress ovarian cancer cells migration and invasion. We hypothesized that SEMA5A expression promotes ovarian cancer invasion and metastasis. We investigated the expression of SEMA5A in patients with metastatic ovarian cancer (n = 43), localized tumor (n = 37) and normal ovarian tissue (n = 12) from non-malignant diseases as control with different histopathological characteristics. For Silencing of SEMA5A in vitro, we treated human ovarian cancer cells (OVCAR-3, A2780/CP70) with miR-27a and miR-27b. We observed significantly higher expression of SEMA5A protein (P= 0.001) in metastatic ovarian cancer tissue associated with poor overall survival outcomes compared to localized ovarian cancer and control. In vitro silencing of SEMA5A reduced migration and invasion of ovarian cancer cell. Our data offer opportunities for the therapeutic modulation and biomarker of metastatic ovarian cancer.

Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways

2012 ◽  
Vol 442 (2) ◽  
pp. 293-302 ◽  
Author(s):  
Ming-Cheng Chang ◽  
Chi-An Chen ◽  
Pao-Jen Chen ◽  
Ying-Cheng Chiang ◽  
Yu-Li Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Tumour Progression ◽  
Cancer Invasion ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Cancer Tissues ◽  
Specific Inhibitors

Ovarian cancer has one of the highest mortalities in malignancies in women, but little is known of its tumour progression properties and there is still no effective molecule that can monitor its growth or therapeutic responses. MSLN (mesothelin), a secreted protein that is overexpressed in ovarian cancer tissues with a poor clinical outcome, has been previously identified to activate PI3K (phosphoinositide 3-kinase)/Akt signalling and inhibit paclitaxel-induced apoptosis. The present study investigates the correlation between MSLN and MMP (matrix metalloproteinase)-7 in the progression of ovarian cancer, and the mechanism of MSLN in enhancing ovarian cancer invasion. The expression of MSLN correlated well with MMP-7 expression in human ovarian cancer tissues. Overexpressing MSLN or ovarian cancer cells treated with MSLN showed enhanced migration and invasion of cancer cells through the induction of MMP-7. MSLN regulated the expression of MMP-7 through the ERK (extracellular-signal-regulated kinase) 1/2, Akt and JNK (c-Jun N-terminal kinase) pathways. The expression of MMP-7 and the migrating ability of MSLN-treated ovarian cancer cells were suppressed by ERK1/2- or JNK-specific inhibitors, or a decoy AP-1 (activator protein 1) oligonucleotide in in vitro experiments, whereas in vivo animal experiments also demonstrated that mice treated with MAPK (mitogen-activated protein kinase)/ERK- or JNK-specific inhibitors could decrease intratumour MMP-7 expression, delay tumour growth and extend the survival of the mice. In conclusion, MSLN enhances ovarian cancer invasion by MMP-7 expression through the MAPK/ERK and JNK signal transduction pathways. Blocking the MSLN-related pathway could be a potential strategy for inhibiting the growth of ovarian cancer.

scholarly journals Long non-coding RNA THOR promotes Ovarian Cancer cells progression via STAT3 pathway

2020 ◽  
Author(s):  
Jing Ge ◽  
Tao Han ◽  
Lili Shan ◽  
Jing Na ◽  
Ya Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Malignant Tumors ◽  
Ovarian Cancer Cells ◽  
Self Renewal ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
The Impact ◽  
Long Non Coding Rna

Abstract Background Ovarian cancer (OC) is one of the most common malignant tumors in the world. The prognosis of OC remains poor due to the advanced stage and distant metastasis at the time of diagnosis. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in OC was still unknown.Methods RT-PCR and western blot analysis were used to detect the expression of THOR and p-STAT3. The impact of THOR on OC proliferation, metastasis and self-renew was investigated in vitro and in vivo . The prognostic value of THOR was determined in OC patient cohorts.Results In this study, our results found that THOR was markedly upregulated in human OC tissues and predict the poor prognosis of OC patients. THOR knockdown resulted in significant inhibition of the growth, metastasis and self-renewal of OC cells. Mechanistically, THOR drives OC cell progression via the STAT3 signaling. Moreover, the specific STAT3 inhibitor S3I-201 diminished the discrepancy in the growth, metastatic and self-renewal capacity between THOR-silenced OC cells and control cells, which further confirmed that STAT3 was required in THOR-driven OC cells progression.Conclusion Our findings revealed that THOR could promote OC cells growth, metastasis and self-renew by activating STAT3 signaling and may be a good predictive factor and therapeutic target.

scholarly journals Long non-coding RNA THOR promotes Ovarian Cancer cells progression via IL-6/STAT3 pathway

2020 ◽  
Author(s):  
Jing Ge ◽  
Tao Han ◽  
Lili Shan ◽  
Jing Na ◽  
Ya Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Malignant Tumors ◽  
Ovarian Cancer Cells ◽  
Self Renewal ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
The Impact ◽  
Long Non Coding Rna

Abstract Background: Ovarian cancer (OC) is one of the most common malignant tumors in the world. The prognosis of OC remains poor due to the advanced stage and distant metastasis at the time of diagnosis. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in OC remains unclear. Methods: RT-PCR and western blot analysis were used to detect the expression of THOR, p-STAT3 and IL-6. The impact of THOR on OC proliferation, metastasis and self-renewal was investigated in vitro and in vivo. The prognostic value of THOR was determined in OC patient cohorts. Results: In this study, our results find that THOR is markedly upregulated in human OC tissues and predicts the poor prognosis of OC patients. Functional studies have revealed that knockdown of THOR inhibits the growth, metastasis and self-renewal of OC cells. Mechanistically, THOR drives OC cell progression via the IL-6/STAT3 signaling. Moreover, the specific STAT3 inhibitor S3I-201 or IL-6R inhibitor tocilizumab diminish the discrepancy in the growth, metastatic and self-renewal capacity between THOR-silenced OC cells and control cells, which further confirm that IL-6/STAT3 is required in THOR-driven OC cells progression. Conclusion: Our findings reveal that THOR could promote OC cells growth, metastasis and self-renewal by activating IL-6/STAT3 signaling and may be a good predictive factor and therapeutic target.

Morin Inhibits Ovarian Cancer Growth through the Inhibition of NF-κB Signaling Pathway

2020 ◽  
Vol 19 (18) ◽  
pp. 2243-2250 ◽  
Author(s):  
Meimei Xu ◽  
Yan Zhang
Keyword(s):  
Ovarian Cancer ◽  
Colony Formation ◽  
Cultured Cells ◽  
Tumor Formation ◽  
Cancer Growth ◽  
Ovarian Cancer Cells ◽  
Therapeutic Drugs ◽  
Underlying Mechanisms

Background &Objective: Ovarian cancer has the highest mortality in gynecological tumors without effective therapeutic drugs as a result of drug-resistance for long-term utilization. Morin has been reported to possess powerful anti-tumor effects in several cancers. The present study aims to investigate whether Morin could influence ovarian cancer growth and underlying mechanisms. Methods: Morin was administered to cultured cells in vitro and formed tumors in vivo. MTT and colony formation assays were performed to explore the effects of Morin on the proliferation and colony formation of OVCAR3 and SKOV3 ovarian cancer cells. Western blot, RT-qPCR, immunofluorescence as well as ELISA were used to detect protein and mRNA expression of target factors. Tumor formation was performed to investigate tumorigenesis ability of drug-treated cells. Results: The proliferation and colony size of OVCAR3 and SKOV3 were significantly decreased after Morin administration. The expression of NF-κB and inflammatory cytokine IL6/8 induced by TNF-α can be inhibited by Morin. Furthermore, Morin inhibited the volume of ovarian cancer tumors in nude mice. Conclusion: Morin effectively alleviates ovarian cancer growth, inhibits the inflammatory response, and reduces tumor size via modulation of the NF-κB pathway.

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