scholarly journals LINC00665 Affects the Malignant Biological Behavior of Ovarian Cancer via the miR-148b-3p/KLF5

2021 ◽  
Author(s):  
Shenglan Wang ◽  
Chuanchuan Liu ◽  
Yongchuan Li ◽  
Jinwan Qiao ◽  
Xinling Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Expression Patterns ◽  
Cell Activity ◽  
Scratch Test ◽  
Biological Behavior ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Klf5 Expression

Abstract Objectives: This study was to investigate the expression and clinical significance of long intergenic noncoding RNA 00665 (LINC00665) in ovarian cancer , as well as its effect on malignant biological behavior of ovarian cancer cells. Methods: The expressions of LINC00665, miR-148b-3p and KLF5 in ovarian cancer (OC) tissues and cells were detected by RT-qPCR. Western blotting was used to detect KLF5 expression. The expression patterns of LINC00665, U6 and GAPDH in nuclear and cytoplasm fractions were detected using qRT-PCR. Besides, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, the interactions between LINC00665 and miR-148b-3p and between miR-148b-3p and KLF5 were verified by luciferase reporter assay, and the correlations among these three genes were analyzed.Results: LINC00665 expression was up-regulated in ovarian cancer cell lines and tissues. Si-LINC00665 inhibited cell proliferation, invasion and migration, and induced the apoptosis to a certain extent. Subcellular fraction assay revealed the location of LINC00665 was mainly situated in the cytoplasm. Besides, miR-148b-3p was a target of LINC00665, and KLF5 was directly targeted by miR-148b-3p. Si-LINC00665 inhibited KLF5 expression, miR-148b-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited LINC00665 expression. Interestingly, expressions of LINC00665 and miR-148b-3p, and expressions of miR-148b-3p and KLF5 were negatively correlated, while expressions of LINC00665 and KLF5 were positively correlated. In addition, si-KLF5 inhibited the malignant biological behavior of ovarian cancer cells, while miR-148b-3p inhibitor had the opposite effect. Most importantly, the si-LINC00665 could reverse the promotion effect of miR-148b-3p inhibitor on the malignant biological behavior of ovarian cancer cells.Conclusions: LINC00665 can be used as an effective prognostic indicator of ovarian cancer, which has the potential to be a new drug target.

scholarly journals LncRNA OIP5-AS1 Affects the Malignant Biological Behavior of Ovarian Cancer via the miR-153-3p/KLF5 Axis

2020 ◽  
Author(s):  
Shenglan Wang ◽  
Chuanchuan Liu ◽  
Yongchuan Li ◽  
Jinwan Qiao ◽  
Xinling Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Expression Patterns ◽  
Cell Activity ◽  
Scratch Test ◽  
Prognostic Indicator ◽  
Biological Behavior ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Klf5 Expression

Abstract Objectives: The purpose of this study was to investigate the expression and clinical significance of LncRNA OIP5-AS1 in ovarian cancer , as well as its effect on malignant biological behavior of ovarian cancer cells. Methods: The expression of OIP5-AS1, miR-153-3p and KLF5 in ovarian cancer (OC) tissues and cells were detected by RT-qPCR. Western Blotting was used to detect KLF5 expression. The expression patterns of OIP5-AS1, U6 and GAPDH in nuclear and cytoplasm fractions were detected using qRT-PCR. Besides, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, The interaction between OIP5-AS1 and miR-153-3p and between miR-153-3p and KLF5 were verified by luciferase reporter assay, and the correlations among these three genes were analyzed.Results: OIP5-AS1 expression was up-regulated in ovarian cancer cell lines and tissues. Si-OIP5-AS1 inhibited cell proliferation, invasion and migration, and induced the apoptosis to a certain extent. Subcellular fraction assay revealed the location of OIP5-AS1 was mainly situated in the cytoplasm. In addition, miR-153-3p was a target of OIP5-AS1, and KLF5 was directly targeted by miR-153-3p. Si-OIP5-AS1 inhibited KLF5 expression, miR-153-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited OIP5-AS1 expression. Interestingly, expression of OIP5-AS1 and miR-153-3p, and expression of miR-153-3p and KLF5 were negatively correlated, while expression of OIP5-AS1 and KLF5 was positively correlated. In addition, si-KLF5 inhibited the malignant biological behavior of ovarian cancer cells, while miR-153-3p inhibitor had the opposite effect. Most importantly, the addition of si-OIP5-AS1 to mir-153-3p silenced cells could reverse the promotion effect of miR-153-3p inhibitor on the malignant biological behavior of ovarian cancer cells.Conclusions: OIP5-AS1 can be used as an effective prognostic indicator of ovarian cancer, which has the potential to be a new drug target.

scholarly journals A Feedback Loop Between miR-30a/c-5p and DNMT1 Mediates Cisplatin Resistance in Ovarian Cancer Cells

2017 ◽  
Vol 41 (3) ◽  
pp. 973-986 ◽  
Author(s):  
Xi Han ◽  
Shuai Zhen ◽  
Zhongxue Ye ◽  
Jiaojiao Lu ◽  
Lijie Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Feedback Loop ◽  
Cisplatin Resistance ◽  
Expression Patterns ◽  
Family Members ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Aberrant Methylation ◽  
Mesenchymal Transition

Background: Many microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression patterns have been suggested to correlate with chemo-resistance of cancer cells. We aim to study the role of miR-30 family members in cisplatin-resistance of ovarian cancer cells. Methods: qRT-PCR was used to compare differential expression levels of miR-30 family members in ovarian cancer cell line A2780 and its cisplatin-resistant derivative CP70. Changes of cisplatin-sensitivity in miR-30a-5p- and miR-30c-5p-overexpressed-CP70 cells and miR-30a-5p- and miR-30c-5p-inhibited-A2780 cells were examined by CCK8 assay and apoptosis analysis using flow cytometry; targets of miR-30a/c-5p were analyzed by western blotting and luciferase reporter assay; methylation regulation of pre-miR-30a/c-5p was examined by methylation specific PCR. Results: miR-30a-5p and miR-30c-5p, in contrast to other miR-30 family members, dramatically decreased in cisplatin-resistant CP70 cells due to overexpressed-DNMT1 induced aberrant methylation. miR-30a/c-5p in turn directly inhibited DNMT1 as well as Snail. Forced expression of miR-30a/c-5p or knocking down of DNMT1 and Snail promoted cisplatin susceptibility and partially reversed epithelial-mesenchymal transition (EMT) in CP70 cells, while inhibition of miR-30a/c-5p or ectopic expression of DNMT1 and Snail induced cisplatin resistance and partial EMT in cisplatin-sensitive A2780 cells. Conclusions: A feedback loop between miR-30a/c-5p and DNMT1 is a potent signature for cisplatin-resistance and EMT in ovarian cancer, promising a potential target for improved anti-cancer treatment.

scholarly journals LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer

2018 ◽  
Vol 49 (4) ◽  
pp. 1289-1303 ◽  
Author(s):  
Lei  Chang ◽  
Ruixia Guo ◽  
Zhongfu Yuan ◽  
Huirong Shi ◽  
Dongya Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Ovarian Cancer Cell Line ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Qrt Pcr ◽  
Gene Assay ◽  
Lncrna Hotair

Background/Aims: The long noncoding RNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been demonstrated to be a vital modulator in the proliferation and metastasis of ovarian cancer cells, but its potential molecular mechanism remains to be elucidated. In the current study, we aimed to uncover the biological role of lncRNA HOTAIR and its underlying regulatory mechanism in the progression and metastasis of ovarian cancer. Methods: HOTAIR expression was detected by quantitative RT-PCR (qRT-PCR) and northern blotting. The SKOV3 ovarian cancer cell line was chosen for the subsequent assays. In addition, the molecular mRNA and protein expression levels were examined by qRT-PCR and western blotting. The competitive endogenous RNA (ceRNA) mechanism was validated by bioinformatics analysis and a dual luciferase reporter gene assay. Results: HOTAIR expression was significantly higher in ovarian carcinoma tissues and cell lines than in the control counterparts. Both CCND1 and CCND2 were downstream targets of miR-206. The inhibition of HOTAIR elevated the expression of miR-206 and inhibited the expression of CCND1 and CCND2. Moreover, CCND1 and CCND2 were highly expressed in ovarian cancer tissues, and their expression was positively correlated with HOTAIR expression. Finally, the functional assays indicated that the anticancer effects of miR-206 could be rescued by the simultaneous overexpression of either CCND1 or CCND2 in ovarian cancer. Conclusion: HOTAIR enhanced CCND1 and CCND2 expression by negatively modulating miR-206 expression and stimulating the proliferation, cell cycle progression, migration and invasion of ovarian cancer cells.

scholarly journals Extracellular vesicle-encapsulated microRNA-424 exerts inhibitory function in ovarian cancer by targeting MYB

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ping Li ◽  
Hongyan Xin ◽  
Lili Lu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Expression Patterns ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Vegf Receptor ◽  
Gene Assay

Abstract Background Recent studies have suggested a crucial role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in ovarian cancer treatment. We, therefore, set out to explore the mechanism through which MSC-derived EVs delivered microRNA-424 (miR-424) to influence the development of ovarian cancer. Methods Bioinformatics analyses were first performed to screen ovarian cancer-related differentially expressed genes and to predict regulatory miRNAs. Then, dual-luciferase reporter gene assay was carried out to verify the relationship between miR-424 and MYB. Subsequently, the characterized MSCs and isolated EVs were co-cultured with ovarian cancer cells, followed by determination of the expression patterns of miR-424, MYB, vascular endothelial growth factor (VEGF), and VEGF receptor (VEGFR), respectively. In addition, the effects of EVs-delivered miR-424 on the proliferation, migration, invasion and tube formation of ovarian cancer cells were assessed using gain- and loss-of-function approaches. Lastly, tumor xenograft was induced in nude mice to illustrate the influence of EVs-loaded miR-424 on ovarian cancer in vivo. Results Our data exhibited that MYB was highly-expressed and miR-424 was poorly-expressed in ovarian cancer. More importantly, MYB was identified as a target gene of miR-424. Additionally, the transfer of miR-424 by MSC-derived EVs was found to repress the proliferation, migration, and invasion of ovarian cancer cells, with a reduction in the expressions of VEGF and VEGFR. Furthermore, MSC-derived EVs over-expressing miR-424 could inhibit the proliferation, migration, and tube formation of human umbilical vein endothelial cells, and also suppressed tumorigenesis and angiogenesis of ovarian tumors in vivo. Conclusion Collectively, our findings indicate that MSC-derived EVs transfer miR-424 to down-regulate MYB, which ultimately led to the inhibition of the tumorigenesis and angiogenesis of ovarian cancer. Hence, this study offers a potential prognostic marker and a therapeutic target for ovarian cancer.

scholarly journals LBX2-AS1 Promotes Ovarian Cancer Progression by Facilitating E2F2 Gene Expression via MIR-455-5P and MIR-491-5P Sponging

2020 ◽  
Author(s):  
Jian Cao ◽  
Huan Wang ◽  
Ranran Tang ◽  
Guangquan Liu ◽  
Pengfei Xu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Colony Formation ◽  
Noncoding Rna ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Cancer Tissue ◽  
Gene Assay

Abstract Background:LBX2-AS1 is a long noncoding RNA that facilitates the development of gastrointestinal cancers and lung cancer, but its participation in ovarian cancer development remained uninvestigated.Methods: Clinical data retrieved from TCGA ovarian cancer database and the clinography of 60 ovarian cancer patients who received anti-cancer treatment in our facility were analyzed. The overall cell growth, colony formation, migration, invasion, apoptosis and tumor formation on nude mice of ovarian cancer cells were evaluated before and after lentiviral-based LBX2-AS1 knockdown. ENCORI platform was used to explore LBX2-AS1-interacting microRNAs and target genes of the candidate microRNAs. Luciferase reporter gene assay and RNA-pulldown assay were used to verify the putative miRNA-RNA interactions.Results: Ovarian cancer tissue specimens showed significant higher LBX2-AS1 expression levels that non-cancerous counterparts. High expression level of LBX2-AS1 significantly associated with patients reduced overall survival. LBX2-AS1 knockdown significantly downregulated the cell growth, colony formation, migration, invasion and tumor formation capacity of ovarian cancer cells and increased their apoptosis in vitro. LBX2-AS1 interacts with and thus inhibits the function of miR-455-5p and miR-491-5p, both of which restrained the expression of E2F2 gene in ovarian cancer cells via mRNA targeting. Transfection of miRNA inhibitors of these two miRNAs or forced expression of E2F2 counteracted the effect of LBX2-AS1 knockdown on ovarian cancer cells.ConclusionsLBX2-AS1 was a novel cancer-promoting lncRNA in ovarian cancer. This lncRNA increased the cell growth, survival, migration, invasion and tumor formation of ovarian cancer cells by inhibiting miR-455-5p and miR-491-5p, thus liberating the expression of E2F2 cancer-promoting gene.

scholarly journals ZNF703 promotes tumor progression in ovarian cancer by interacting with HE4 and epigenetically regulating PEA15

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Shuang Wang ◽  
Caixia Wang ◽  
Yuexin Hu ◽  
Xiao Li ◽  
Shan Jin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Nuclear Translocation ◽  
Biological Behavior ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells

Abstract Background It is known that the transcription factor zinc finger protein 703 (ZNF703) plays an important role in physiological functions and the occurrence and development of various tumors. However, the role and mechanism of ZNF703 in ovarian cancer are unclear. Materials and methods Immunohistochemistry was used to analyze the expression of ZNF703 in ovarian cancer patients and to assess the effect of ZNF703 expression on the survival and prognosis of ovarian cancer patients. ZNF703 overexpression and suppression expression experiments were used to evaluate the effect of ZNF703 on malignant biological behavior of ovarian cancer cells in vitro. Detecting the interaction between HE4 and ZNF703 by immunofluorescence colocalization and coprecipitation, and nuclear translocation. Chromatin immunoprecipitation-sequencing (ChIP-Seq), dual luciferase reporter assay, ChIP-PCR, in vivo model were applied to study the molecular mechanism of ZNF703 affecting the development of ovarian cancer. Results ZNF703 was highly expressed in ovarian cancer tissues, and its expression level is related to the prognosis of ovarian cancer patients. In vivo and in vitro experiments confirmed that ZNF703 overexpression/inhibition expression will promoted/inhibited the malignant biological behavior of ovarian cancer. Mechanically, ZNF703 interacted with HE4, and HE4 promoted nuclear translocation of ZNF703. ChIP-Seq identified multiple regulatory targets of ZNF703, of which ZNF703 directly binds to the enhancer region of PEA15 to promote the transcription of PEA15 and thereby promoted the proliferation of cancer cells. Conclusion The results showed that ZNF703 as an oncogene played an important role in the epigenetic modification of ovarian cancer proliferation, and suggested that ZNF703 as a transcription factor may become a prognostic factor and a potential therapeutic target for ovarian cancer.

Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

2019 ◽  
Vol 19 (4) ◽  
pp. 473-486 ◽  
Author(s):  
Katarzyna Bednarska-Szczepaniak ◽  
Damian Krzyżanowski ◽  
Magdalena Klink ◽  
Marek Nowak
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Biology ◽  
Immune Cell ◽  
Immunosuppressive Agents ◽  
Cell Activity ◽  
Ovarian Cancer Cells ◽  
Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

scholarly journals Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Huan Lu ◽  
Guanlin Zheng ◽  
Xiang Gao ◽  
Chanjuan Chen ◽  
Min Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Rna Binding ◽  
Erk Signaling ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Vacuolar Protein

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

scholarly journals Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qingjuan Meng ◽  
Ningning Wang ◽  
Guanglan Duan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Invasion And Migration ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna

Abstract Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

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