scholarly journals The Cancer-Testis Long Non-coding RNA PCAT6 Facilitates the Malignant Phenotype of Ovarian Cancer by Sponging miR-143-3p

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaofang Tan ◽  
Yang Shao ◽  
Yue Teng ◽  
Siyu Liu ◽  
Weijian Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transforming Growth Factor ◽  
Progression Free Survival ◽  
Bioinformatic Analysis ◽  
Migration And Invasion ◽  
Small Rna Sequencing ◽  
Loss Of Function ◽  
Poor Overall Survival ◽  
Inhibition Of Proliferation ◽  
Skov3 Cells

Background: It has been reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis. However, their roles in ovarian cancer (OC) remain to be elucidated. The aim of this study was to uncover the function and underlying mechanisms of PCAT6 in OC.Methods: The expression pattern of PCAT6 in OC was analyzed in the GSE137238, GSE143897 and Gene Expression Profile Interactive Analysis (GEPIA) datasets. Kaplan–Meier Plotter online software was used for survival analysis. Loss-of-function assays and gain-of-function assays were used to assess the function of PCAT6 in OC development. Moreover, small-RNA sequencing, bioinformatic analysis, luciferase assays and rescue experiments were carried out to clarify the potential mechanism of PCAT6 in OC.Results: PCAT6 expression was significantly increased in OC tissues and positively correlated with advanced stages and with poor overall survival, progression-free survival and post-progression survival. Knockdown of PCAT6 in A2780 and SKOV3 cells inhibited OC cell proliferation, migration and invasion. In contrast, Overexpression of PCAT6 exerted the opposite effects on OC cells. Notably, PCAT6 bound to miR-143-3p and affected the expression of transforming growth factor (TGF)-β-activated kinase 1 (TAK1). Subsequent rescue assays confirmed that upregulation of miR-143-3p decreased the PCAT6 overexpression-induced promotion of proliferation, migration and invasion. Moreover, downregulation of miR-143-3p reversed the PCAT6 knockdown-induced inhibition of proliferation, migration, and invasion.Conclusions: Our findings demonstrate that PCAT6 plays an oncogenic role in OC and may be useful as a therapeutic target for OC.

Long Noncoding RNA LINC00858 Promotes the Progression of Ovarian Cancer via Regulating the miR-134-5p/TRIM44 Axis

2020 ◽  
Author(s):  
Ning Wang ◽  
Qin-Xue Cao ◽  
Jun Tian ◽  
Lu Ren ◽  
Hai-Ling Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Cancer Tissue ◽  
Loss Of Function ◽  
Ovarian Cancer Tissue ◽  
Skov3 Cells ◽  
Tissue Specimens

Abstract Background Ovarian cancer remains one of the most challenging areas of cancer research. Recent studies have shown that many long non-coding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and involved in the pathological progress of ovarian cancer. In the present study, we aimed to investigate the role of lncRNA LINC00858 and the potential mechanism in ovarian cancer. Methods The qRT-PCR was used to measure the expression levels of LINC00858 and miR-134-5p in ovarian cancer tissue specimens and cell lines. Loss-of-function assays were performed to investigate the role of LINC00858 in ovarian cancer progression. MTT assay was carried out to measure cell proliferation. Transwell assays were performed to determine the migration and invasion of ovarian cancer cells. Biological information analysis and luciferase report gene assay were used to verify potential downstream genes of LINC00858. The xenograft mouse model was established to analyze tumor growth in vivo. Results Our results showed that LINC00858 was highly expressed in human ovarian cancer tissue specimens and cell lines. Loss-of-function assays showed that knockdown of LINC00858 significantly inhibited cell proliferation, migration and invasion of SKOV3 cells, and suppressed tumor growth in mouse xenograft models. Mechanistic studies revealed that LINC00858 acted as a sponge of miR-134-5p and then regulated the expression TRIM44 in SKOV3 cells. Furthermore, rescue experiments illustrated that inhibition of miR-134-5p restored the inhibitory effects of LINC00858 knockdown on ovarian cancer cell proliferation, migration and invasion. TRIM44 overexpression could counteract the inhibitory effects of miR-134-5p mimics on ovarian cancer cells. Conclusion In conclusion, these findings demonstrated that LINC00858 exerted oncogenic role in ovarian cancer, which was mediated by miR-134-5p/TRIM44 axis. Thus, LINC00858 might be a therapeutic target for the treatment of ovarian cancer.

scholarly journals Oncological Effects and Prognostic Value of AMAP1 in Gastric Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiao Li ◽  
Shan Tian ◽  
Yingyun Guo ◽  
Weiguo Dong
Keyword(s):  
Gastric Cancer ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Bioinformatic Analysis ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Diagnostic Significance ◽  
Poor Overall Survival ◽  
Normal Tissues

PurposeWe examined the diagnostic significance, prognostic value, and potential function of AMAP1 in gastric cancer (GC).MethodsComprehensive bioinformatic analysis was conducted to investigate differential expression of AMAP1 mRNA and protein in GC. Meta-analyses were utilized to determine the overall prognostic correlation of AMAP1 mRNA in patients with GC. A panel of vitro assays was applied to assess target microRNA and AMAP1 protein in GC cell lines and tissues, respectively.ResultsAMAP1 mRNA and protein levels were upregulated in GC specimens, compared to matched normal tissues. AMAP1 mRNA exhibited promising results regarding differential diagnosis of GC and normal tissue. Meta-analysis based on the TCGA and GEO databases revealed that high AMAP1 mRNA abundance was associated with poor overall survival (HR = 1.42; 95% CI: 1.06–1.89) and was correlated with reduced progression-free survival (HR = 1.89; 95% CI: 1.51–2.36) in GC patients. Moreover, AMAP1 was negatively correlated with miR-192-3p (r = −0.3843; P < 0.0001). A dual-luciferase assay revealed that miR-192-3p targeted AMAP1. Levels of miR-192-3p were significantly higher in GC tissues and GC cells than in normal tissues and cells. Moreover, AMAP1 silencing resulted in reduced GC proliferation, migration, and invasion.ConclusionAMAP1 is a novel oncogene in GC and is negatively correlated with by miR-192-3p. AMAP1 may act as a diagnostic and prognostic marker of GC.

scholarly journals FBXO6-mediated RNASET2 ubiquitination and degradation governs the development of ovarian cancer

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Mei Ji ◽  
Zhao Zhao ◽  
Yue Li ◽  
Penglin Xu ◽  
Jia Shi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Inverse Correlation ◽  
Degradation Pathway ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Poor Overall Survival ◽  
Protein Levels ◽  
Ubiquitin E3 Ligase ◽  
Ovarian Tumorigenesis ◽  
F Box Protein

AbstractRNASET2 (Ribonuclease T2) functions as a tumor suppressor in preventing ovarian tumorigenesis. However, the mechanisms underlying the regulation of RNASET2 protein are completely unknown. Here we identified the F-box protein FBXO6, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the ubiquitin E3 ligase for RNASET2. We found that the interaction between FBXO6 and RNASET2 induced RNASET2 instability through the ubiquitin-mediated proteasome degradation pathway. FBXO6 promoted K48-dependent ubiquitination of RNASET2 via its FBA domain. Through analysis of the TCGA dataset, we found that FBXO6 was significantly increased in ovarian cancer tissues and the high expression of FBXO6 was related to the poor overall survival (OS) of ovarian cancer patients at advanced stages. An inverse correlation between the protein levels of FBXO6 and RNASET2 was observed in clinic ovarian cancer samples. Depletion of FBXO6 promoted ovarian cancer cells proliferation, migration, and invasion, which could be partially reversed by RNASET2 silencing. Thus, our data revealed a novel FBXO6-RNASET2 axis, which might contribute to the development of ovarian cancer. We propose that inhibition of FBXO6 might represent an effective therapeutic strategy for ovarian cancer treatment.

scholarly journals LY2157299 Monohydrate, a TGF-βR1 Inhibitor, Suppresses Tumor Growth and Ascites Development in Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 260 ◽  
Author(s):  
Qing Zhang ◽  
Xiaonan Hou ◽  
Bradley Evans ◽  
Jamison VanBlaricom ◽  
Saravut Weroha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cell Lines ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Migration And Invasion ◽  
Ascites Formation ◽  
Tgf Β1

Transforming growth factor beta (TGF-β) signaling has pleiotropic functions regulating cancer initiation, development, and metastasis, and also plays important roles in the interaction between stromal and cancer cells, making the pathway a potential therapeutic target. LY2157299 monohydrate (LY), an inhibitor of TGF-β receptor I (TGFBRI), was examined for its ability to inhibit ovarian cancer (OC) growth both in high-grade serous ovarian cancer (HGSOC) cell lines and xenograft models. Immunohistochemistry, qRT-PCR, and Western blot were performed to study the effect of LY treatment on expression of cancer- and fibroblast-derived genes. Results showed that exposure to TGF-β1 induced phosphorylation of SMAD2 and SMAD3 in all tested OC cell lines, but this induction was suppressed by pretreatment with LY. LY alone inhibited the proliferation, migration, and invasion of HGSOC cells in vitro. TGF-β1-induced fibroblast activation was blocked by LY. LY also delayed tumor growth and suppressed ascites formation in vivo. In addition, independent of tumor inhibition, LY reduces ascites formation in vivo. Using OVCAR8 xenograft specimens we confirmed the inhibitory effect of LY on TGF-β signaling and tumor stromal expression of collagen type XI chain 1 (COL11A1) and versican (VCAN). These observations suggest a role for anti-TGF-β signaling-directed therapy in ovarian cancer.

scholarly journals NFATc1 regulates cell proliferation, migration, and invasion of ovarian cancer SKOV3 cells in vitro and in vivo

2016 ◽  
Vol 36 (2) ◽  
pp. 918-928 ◽  
Author(s):  
Long Li ◽  
Zhaoning Duan ◽  
Jihui Yu ◽  
Hong-Xing Dang
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Migration And Invasion ◽  
Skov3 Cells

scholarly journals MicroRNA-338-3p suppresses ovarian cancer cells growth and metastasis: implication of Wnt/catenin beta and MEK/ERK signaling pathways

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Ruitao Zhang ◽  
Huirong Shi ◽  
Fang Ren ◽  
Wei Feng ◽  
Yuan Cao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Target Genes ◽  
Erk Signaling ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Inhibition Of Proliferation ◽  
Mesenchymal Transition ◽  
Biomedical Databases

Abstract Background Downregulation of microRNA-338-3p (miR-338-3p) was detected in many malignant tumors, which indicated miR-338-3p might serve as a role of antioncogene in those cancers. The present study aimed to explore the roles of miR-338-3p in the growth and metastasis of ovarian cancer cells and elaborate the underlying possible molecular mechanism. Methods Multiply biomedical databases query and KEGG pathway enrichment assay were used to infilter possible target genes and downstream pathways regulated by miR-338-3p. Overexpression miR-338-3p lentiviral vectors were transfected into ovarian cancer OVCAR-3 and OVCAR-8 cells, cell proliferation, migration and invasion were analyzed by MTT, colony formation, transwell, Matrigel assay and xenograft mouse model. One 3′-untranslated regions (UTRs) binding target gene of miR-338-3p, MACC1 (MET transcriptional regulator MACC1), and its regulated gene MET and downstream signaling pathway activities were examined by western blot. Results Biomedical databases query indicated that miR-338-3p could target MACC1 gene and regulate Met, downstream Wnt/Catenin beta and MEK/ERK pathways. Rescue of miR-338-3p could inhibit the proliferation, migration and invasion of ovarian cancer cells, and suppress the growth and metastasis of xenograft tumor. Restoration of miR-338-3p could attenuate MACC1 and Met overexpression induced growth, epithelial to mesenchymal transition (EMT) and activities of Wnt/Catenin beta and MEK/ERK signaling in vitro and in vivo. Conclusions The present data indicated that restoration of miR-338-3p could suppress the growth and metastasis of ovarian cancer cells, which might due to the inhibition of proliferation and EMT induced by MACC1, Met and its downstream Wnt/Catenin beta and MEK/ERK signaling pathways.

scholarly journals Genome-scale CRISPR knockout screen identifies TIGAR as a modifier of PARP inhibitor sensitivity

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Pingping Fang ◽  
Cristabelle De Souza ◽  
Kay Minn ◽  
Jeremy Chien
Keyword(s):  
Ovarian Cancer ◽  
Metabolic Pathways ◽  
Clinical Utility ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Loss Of Function ◽  
Poor Overall Survival ◽  
Cytotoxic Effects ◽  
Cancer Types ◽  
Genome Scale

Abstract Treatment of cancer with poly (ADP-ribose) polymerase (PARP) inhibitors is currently limited to cells defective in the homologous recombination (HR) pathway. Identification of genetic targets that induce or mimic HR deficiencies will extend the clinical utility of PARP inhibitors. Here we perform a CRISPR/Cas9-based genome-scale loss-of-function screen, using the sensitivity of PARP inhibitor olaparib as a surrogate. We identify C12orf5, encoding TP53 induced glycolysis and apoptosis regulator (TIGAR), as a modifier of PARP inhibitor response. We show that TIGAR is amplified in several cancer types, and higher expression of TIGAR associates with poor overall survival in ovarian cancer. TIGAR knockdown enhances sensitivity to olaparib in cancer cells via downregulation of BRCA1 and the Fanconi anemia pathway and increases senescence of these cells by affecting metabolic pathways and increasing the cytotoxic effects of olaparib. Our results indicate TIGAR should be explored as a therapeutic target for treating cancer and extending the use of PARP inhibitors.

scholarly journals MicroRNA-139-5p Inhibits Cell Proliferation and Invasion by Targeting RHO-Associated Coiled-Coil-Containing Protein Kinase 2 in Ovarian Cancer

2018 ◽  
Vol 26 (3) ◽  
pp. 411-420 ◽  
Author(s):  
Yanli Wang ◽  
Jia Li ◽  
Chunling Xu ◽  
Xiaomeng Zhang
Keyword(s):  
Ovarian Cancer ◽  
Protein Kinase ◽  
Coiled Coil ◽  
Figo Stage ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Poor Overall Survival

Increasing evidence indicates that the dysregulation of microRNAs is associated with the development and progression of various cancers. MicroRNA-139-5p (miR-139-5p) has been reported to have a tumor suppressive role in many types of cancers. The role of miR-139-5p in ovarian cancer (OC) is poorly understood. The purpose of the present study was to explore the expression of miR-139-5p and its function in OC. The results showed that miR-139-5p expression was markedly downregulated in OC tissues and cell lines. In addition, underexpression of miR-139-5p was significantly associated with FIGO stage, lymph mode metastasis, and poor overall survival of OC patients. Functional analyses indicated that overexpression of miR-139-5p significantly inhibited proliferation, colony formation, migration, and invasion of OC cells. Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) was identified as a direct target of miR-139-5p using luciferase reporter assays, qualitative real-time reverse transcriptase PCR (qRT-PCR), and Western blot. In addition, ROCK2 expression was upregulated and was inversely correlated with miR-139-5p levels in OC tissues. Rescue experiments showed that overexpression of ROCK2 effectively reversed the inhibitory effect of OC cells induced by miR-139-5p. Most interestingly, in vivo studies indicated that miR-139-5p markedly suppressed the growth of tumors by repressing ROCK2 expression in nude mice. Taken together, these findings demonstrated that miR-139-5p plays an important tumor suppressor role in OC by directly binding to ROCK2, providing a novel target for the molecular treatment of OC.

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