scholarly journals PAX2 Induces Tubular-Like Structures in Normal and Ovarian Cancer Cells

2020 ◽  
Author(s):  
Kholoud Alwosaibai ◽  
Ensaf Munawer Al-Hujaily ◽  
Salmah Alamri ◽  
Kenneth Garson ◽  
Barbara C. Vanderhyden
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Cells ◽  
Cancer Progression ◽  
Ovarian Cancer Cells ◽  
Ovarian Surface Epithelial ◽  
Vascular Channels ◽  
Ovarian Epithelial Cells

AbstractIn adult tissues, PAX2 protein is expressed in normal oviductal epithelial cells but not in normal ovarian surface epithelial cells. Studies have reported that PAX2 is expressed in a subset of serous ovarian carcinoma cases but the role of PAX2 in the initiation and progression of ovarian cancer remains unknown. The aim of this study was to understand the biological consequences of Pax2 expression in normal and cancerous mouse epithelial (MOSE) cells. We found that Pax2 overexpression in both normal and cancerous ovarian epithelial cells induced the formation of vascular channels both in vitro and in vivo. The results indicate a possible contribution of PAX2 to ovarian cancer progression by increasing the vascular channels to supply nutrients to the tumor cells.

scholarly journals RAC1/miR-3613/RAC1 feedback loop contributes to ovarian cancer progression

2021 ◽  
Author(s):  
Changzhong Li ◽  
Ruobing Leng ◽  
Yunfang Meng ◽  
Na Li ◽  
Feifei Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Negative Feedback Loop

Abstract The RAC1 signal pathway is involved in various tumor cell biological processes. Here, the role of RAC1-miR-3613-RAC1 negative feedback loop in ovarian cancer was explored. Results showed that RAC1 knockdown up-regulated miR-3613, which in turn inhibited RAC1 expression. RAC1 counteracted the inhibitory effect of miR-3613 on the proliferation and invasion of ovarian cancer cells in vitro and on the tumor growth in vivo. In ovarian cancer, miR-3613 expression was negatively correlated with RAC1, and patients with low miR-3613 expression had poor prognosis. These findings indicate the role of RAC1-miR-3613-RAC1 negative feedback loop in the malignant progression of ovarian cancer and its possible therapeutic values.

scholarly journals METTL3 promotes the initiation and metastasis of ovarian cancer by inhibiting CCNG2 expression via promoting the maturation of pri-microRNA-1246

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xuehan Bi ◽  
Xiao Lv ◽  
Dajiang Liu ◽  
Hongtao Guo ◽  
Guang Yao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
High Expression ◽  
Ovarian Cancer Cells ◽  
Inadequate Knowledge ◽  
And Migration ◽  
Cancer Tissues

AbstractOvarian cancer is a common gynecological malignant tumor with a high mortality rate and poor prognosis. There is inadequate knowledge of the molecular mechanisms underlying ovarian cancer. We examined the expression of methyltransferase-like 3 (METTL3) in tumor specimens using RT-qPCR, immunohistochemistry, and Western blot analysis, and tested the methylation of METTL3 by MSP. Levels of METTL3, miR-1246, pri-miR-1246 and CCNG2 were then analyzed and their effects on cell biological processes were also investigated, using in vivo assay to validate the in vitro findings. METTL3 showed hypomethylation and high expression in ovarian cancer tissues and cells. Hypomethylation of METTL3 was pronounced in ovarian cancer samples, which was negatively associated with patient survival. Decreased METTL3 inhibited the proliferation and migration of ovarian cancer cells and promoted apoptosis, while METTL3 overexpression exerted opposite effects. Mechanistically, METTL3 aggravated ovarian cancer by targeting miR-1246, while miR-1246 targeted and inhibited CCNG2 expression. High expression of METTL3 downregulated CCNG2, promoted the metabolism and growth of transplanted tumors in nude mice, and inhibited apoptosis. The current study highlights the promoting role of METTL3 in the development of ovarian cancer, and presents new targets for its treatment.

scholarly journals Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel

2019 ◽  
Vol 20 (5) ◽  
pp. 1042 ◽  
Author(s):  
Apriliana Cahya Khayrani ◽  
Hafizah Mahmud ◽  
Aung Ko Ko Oo ◽  
Maram H. Zahra ◽  
Miharu Oze ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stem Cell Marker ◽  
Ovarian Cancer Cells ◽  
Cancer Therapies ◽  
Ovarian Cancer Cell Lines ◽  
Tumor Selective

Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15–20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies.

scholarly journals Metalloproteinases in Ovarian Cancer

2021 ◽  
Vol 22 (7) ◽  
pp. 3403
Author(s):  
Preston Carey ◽  
Ethan Low ◽  
Elizabeth Harper ◽  
M. Sharon Stack
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Ovarian Cancer Cells ◽  
Age Related ◽  
The Matrix ◽  
Interaction Stress

Proteases play a crucial role in the progression and metastasis of ovarian cancer. Pericellular protein degradation and fragmentation along with remodeling of the extracellular matrix (ECM) is accomplished by numerous proteases that are present in the ovarian tumor microenvironment. Several proteolytic processes have been linked to cancer progression, particularly those facilitated by the matrix metalloproteinase (MMP) family. These proteases have been linked to enhanced migratory ability, extracellular matrix breakdown, and development of support systems for tumors. Several studies have reported the direct involvement of MMPs with ovarian cancer, as well as their mechanisms of action in the tumor microenvironment. MMPs play a key role in upregulating transcription factors, as well as the breakdown of structural proteins like collagen. Proteolytic mechanisms have been shown to enhance the ability of ovarian cancer cells to migrate and adhere to secondary sites allowing for efficient metastasis. Furthermore, angiogenesis for tumor growth and development of metastatic implants is influenced by upregulation of certain proteases, including MMPs. While proteases are produced normally in vivo, they can be upregulated by cancer-associated mutations, tumor–microenvironment interaction, stress-induced catecholamine production, and age-related pathologies. This review outlines the important role of proteases throughout ovarian cancer progression and metastasis.

scholarly journals Down-regulation of ZNF252P-AS1 alleviates ovarian cancer progression by binding miR-324-3p to downregulate LY6K

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Li Geng ◽  
Zhongqiu Wang ◽  
Yongju Tian
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
In Vivo Experiments ◽  
Cancer Tissues

Abstract Background Ovarian cancer is a common gynecological malignant disease in women. Our work aimed to study the specific functions of ZNF252P antisense RNA 1 (ZNF252P-AS1) in ovarian cancer. Methods ZNF252P-AS1, miR-324-3p, and lymphocyte antigen 6 family member K (LY6K) expression were analyzed by bioinformatics tools in ovarian cancer tissues and was quantified by qRT-PCR in ovarian cancer cells. The effect of ZNF252P-AS1 knockdown, miR-324-3p suppression, and LY6K over-expression on apoptosis, cell viability, invasion, migration, and epithelial to mesenchymal transition (EMT) was determined in vitro by using colony formation and EdU assays, flow cytometry, transwell assay, and Western blot. The interactions between ZNF252P-AS1 and miR-324-3p and between miR-324-3p and LY6K were validated by luciferase assays. The effects of restraining ZNF252P-AS1 in vivo were studied using BALB/c male nude mice. Results ZNF252P-AS1 and LY6K levels were up-regulated, while miR-324-3p was declined in ovarian cancer tissues and cells. ZNF252P-AS1 knockdown reduced ovarian cancer cell proliferation, invasion, migration, and EMT, whereas promoted its apoptosis. Besides, ZNF252P-AS1 interacted with miR-324-3p and reversely regulated its level, and miR-324-3p was directly bound to LY6K and negatively regulated its expression. Moreover, ZNF252P-AS1 knockdown reversed the effect of miR-324-3p on cancer cell apoptosis, growth, migration, invasion, and EMT. Similar results were discovered in the rescue experiments between miR-324-3p and LY6K. Additionally, mouse models in vivo experiments further validated that ZNF252P-AS1 knockdown distinctly inhibited tumor growth. Conclusion ZNF252P-AS1 mediated miR-324-3p/LY6K signaling to facilitate progression of ovarian cancer.

scholarly journals Knockdown of TRIM44 inhibits the progression of human epithelial ovarian cancer via the FOXM1-EZH2 signaling pathway

2021 ◽  
Author(s):  
Fanling Meng ◽  
Jing Ding ◽  
Xihai Chen ◽  
Lin Sui ◽  
Yuanlong Hu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Tumor Model ◽  
Ovarian Cancer Cells ◽  
In Vitro Proliferation

Abstract Background. Tripartite motif‑containing protein 44 (TRIM44) was recently identified as a novel oncogene that is overexpressed in several types of human cancers. However, the biological functions of TRIM44 in epithelial ovarian cancer (EOC) remain unclear. Here, we aimed to investigate the role of TRIM44 in EOC and its clinical implications.Methods. The expression of TRIM44 in different ovarian cancer cell lines were detected by western blot. TRIM44 was knocked down by shRNA transfection. The in vitro proliferation, invasion, migration and apoptosis of ovarian cancer cells were detected by CCK8, colony formation assay, transwell filters, tube formation assay and flow cytometry analysis, respectively. The growth ability of xenograft tumors in vivo was examined by a nude mouse metastatic tumor model. Finally, we carried out gene chip analysis and IPA to analyze the potential gene network.Results. High expression of TRIM44 was observed in EOC tissues and cell lines. Knockdown of TRIM44 expression substantially suppressed the proliferation, migration, invasion and colony-forming ability of EOC cells in vitro and attenuated tumor growth in vivo. Mechanistic studies showed that silencing TRIM44 dramatically down regulated the expression of FOXM1, EZH2, CCNE2, CCND3 and BIRC5 in EOC cells, at least in part through inactivation of the FOXM1-EZH2 signaling pathway.Conclusion. Collectively, these data suggest that TRIM44 downregulation inhibits the progression of EOC cells through the suppression of the FOXM1-EZH2 signaling pathway. These results provide novel insight into the role of TRIM44 in tumorigenesis and suggest it could be a potential therapeutic target of ovarian carcinoma.

scholarly journals UNC-45A is preferentially expressed in epithelial cells and binds to and co-localizes with interphase MTs

2019 ◽  
Author(s):  
Juri Habicht ◽  
Ashley Mooneyham ◽  
Mihir Shetty ◽  
Xiaonan Zhang ◽  
Vijayalakshmi Shridhar ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ovarian Cancer Cells ◽  
Mitotic Spindles ◽  
Cellular Processes ◽  
Interphase Cells ◽  
Associated Proteins ◽  
Chemotherapeutic Treatment

AbstractUNC-45A is a ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system. However, emerging studies from both our and other laboratories support a role of UNC-45A outside of actomyosin regulation. This includes studies showing that UNC-45A: regulates gene transcription, co-localizes and biochemically co-fractionates with gamma tubulin and regulates centrosomal positioning, is found in the same subcellular fractions where MT-associated proteins are, and is a mitotic spindle-associated protein with MT destabilizing activity in absence of the actomyosin system.Here, we extended our previous findings and show that UNC45A is variably expressed across a spectrum of cell lines with the highest level being found in HeLa cells and in ovarian cancer cells inherently paclitaxel-resistant. Furthermore, we show that UNC-45A is preferentially expressed in epithelial cells, localizes to mitotic spindles in clinical tumor specimens of cancer and co-localizes and co-fractionates with MTs in interphase cells independent of actin or myosin.In sum, we report alteration of UNC45A localization in the setting of chemotherapeutic treatment of cells with paclitaxel, and localization of UNC45A to MTs both in vitro and in vivo. These findings will be important to ongoing and future studies in the field that further identify the important role of UNC45A in cancer and other cellular processes.

scholarly journals FBW7 suppresses ovarian cancer development by targeting the N6-methyladenosine binding protein YTHDF2

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fei Xu ◽  
Jiajia Li ◽  
Mengdong Ni ◽  
Jingyi Cheng ◽  
Haiyun Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Biological Effects ◽  
Ovarian Cancer Cells ◽  
Promoting Effect ◽  
In Vivo Models ◽  
Cancer Cell Survival ◽  
Cancer Tissues

Abstract Background The tumor suppressor FBW7 is the substrate recognition component of the SCF E3-ubiquitin ligase complex that mediates proteolytic degradation of various oncogenic proteins. However, the role of FBW7 in ovarian cancer progression remains inadequately understood. Methods IP-MASS, co-IP, immunohistochemistry, and western blotting were used to identify the potential substrate of FBW7 in ovarian cancer. The biological effects of FBW7 were investigated using in vitro and in vivo models. LC/MS was used to detect the m6A levels in ovarian cancer tissues. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of YTHDF2. Results We unveil that FBW7 is markedly down-regulated in ovarian cancer tissues and its high expression is associated with favorable prognosis and elevated m6A modification levels. Consistently, ectopic FBW7 inhibits ovarian cancer cell survival and proliferation in vitro and in vivo, while ablation of FBW7 empowers propagation of ovarian cancer cells. In addition, the m6A reader protein, YTHDF2, is identified as a novel substrate for FBW7. FBW7 counteracts the tumor-promoting effect of YTHDF2 by inducing proteasomal degradation of the latter in ovarian cancer. Furthermore, YTHDF2 globally regulates the turnover of m6A-modified mRNAs, including the pro-apoptotic gene BMF. Conclusions Our study has demonstrated that FBW7 suppresses tumor growth and progression via antagonizing YTHDF2-mediated BMF mRNA decay in ovarian cancer.

scholarly journals Splicing Factor DDX23, Transcriptionally Activated by E2F1, Promotes Ovarian Cancer Progression by Regulating FOXM1

2021 ◽  
Vol 11 ◽  
Author(s):  
Chen Zhao ◽  
Yingwei Li ◽  
Chunping Qiu ◽  
Jingying Chen ◽  
Huan Wu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Mrna Processing ◽  
Splicing Factor ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Rna Helicases ◽  
Dead Box

Ovarian carcinoma remains the most lethal gynecological carcinoma. Abnormal expression of splicing factors is closely related to the occurrence and development of tumors. The DEAD-box RNA helicases are important members of the splicing factor family. However, their role in the occurrence and progression of ovarian cancer is still unclear. In this study, we identified DEAD-box helicase 23 (DDX23) as a key DEAD-box RNA helicase in ovarian cancer using bioinformatics methods. We determined that DDX23 was upregulated in ovarian cancer and its high expression predicted poor prognosis. Functional assays indicated that DDX23 silencing significantly impeded cell proliferation/invasion in vitro and tumor growth in vivo. Mechanistically, transcriptomic analysis showed that DDX23 was involved in mRNA processing in ovarian cancer cells. Specifically, DDX23 regulated the mRNA processing of FOXM1. DDX23 silencing reduced the production of FOXM1C, the major oncogenic transcript of FOXM1 in ovarian cancer, thereby decreasing the FOXM1 protein expression and attenuating the malignant progression of ovarian cancer. Rescue assays indicated that FOXM1 was a key executor in DDX23-induced malignant phenotype of ovarian cancer. Furthermore, we confirmed that DDX23 was transcriptionally activated by the transcription factor (TF) E2F1 in ovarian cancer using luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. In conclusion, our study demonstrates that high DDX23 expression is involved in malignant behavior of ovarian cancer and DDX23 may become a potential target for precision therapy of ovarian cancer.

scholarly journals LINC00494 Promotes Ovarian Cancer Development and Progression by Modulating NFκB1 and FBXO32

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Shu ◽  
He Zhang ◽  
Jinqiu Li ◽  
Yanhong Shan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Cancer Pathogenesis ◽  
Potential Interactions

BackgroundOvarian cancer represents one of the most frequent gynecological cancers and is significant cause of death for women around the world. Long non-coding RNAs (lncRNAs) are recognized as critical governors of gene expression during carcinogenesis, but their effects on the occurrence and development of ovarian cancer require further investigation. In this report, we characterized LINC00494 as a novel oncogenic lncRNA in ovarian cancer.MethodsBioinformatics analysis predicted potential interactions among LINC00494, NFκB1, and FBXO32 in ovarian cancer, which were tested by dual-luciferase reporter assay, RNA pull-down, RIP, and ChIP assay. Cancer cells were transfected with relevant treated plasmids, followed by scratch and Transwell assays. The treated cells were injected into nude mice to establish a xenograft model for testing effects of LINC00494 and its target gene in vivo.ResultsLINC00494 and NFκB1 were highly expressed whereas FBXO32 had low expression in ovarian cancer cells and tissues. LINC00494 was found to bind NFκB1 and increase its activity, while NFκB1 was enriched at the FBXO32 promoter region, where it acted to reduce FBXO32 transcription. Overexpression of LINC00494 elevated NFκB1 expression and enhanced cell migration, invasion and tumorigenesis, but additional overexpression of FBXO32 interfered with the tumorgenicity of ovarian cancer cells in vitro and in vivo.ConclusionOur work demonstrated that LINC00494 promoted ovarian cancer progression by modulating FBXO32 via binding with the transcription factor NFκB1. These results provided new insight into the mechanism of ovarian cancer pathogenesis and suggested new therapeutic targets.

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