HO-8910 Cells Research Articles

Exosome-mediated transfer of CD44 from high-metastatic ovarian cancer cells promotes migration and invasion of low-metastatic ovarian cancer cells

ObjectiveTo investigate the detailed roles and mechanisms of tumor-derived exosomes in progression and metastasis of ovarian cancer in vitro.MethodsExosomes were isolated by differential centrifugation method; the morphology, size and biological markers of exosomes were separately defined by transmission electron microscopy, nanoS90 and Western blotting; Trans-well chambers assay was used to assess the ability of migration and invasion of recipient cells uptaking the exosomes from HO8910PM cells. The downstream molecule was screened by mass spectrometry.CD44 was identified by western blotting and the function of CD44 was identified by trans-well chambers assay and CCK8 assay.ResultsExosomes derived from HO8910PM cells could be transferred to HO8910 cells and promote cell migration and invasion in the recipient cells of ovarian cancer. And CD44 could be transferred to the HO8910 cells through exosomes from HO8910PM cells and influence the migration and invasion ability of HO8910 cells.ConclusionThe more aggressive subpopulation can transfer a metastatic phenotype to the less one via secreting exosomes within a heterogeneous tumor. CD44 may be a potential therapeutic approach for ovarian cancer.

Inhibition of long non-coding RNA XIST upregulates microRNA-149-3p to repress ovarian cancer cell progression

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play critical roles in human diseases. We aimed to clarify the role of lncRNA X-inactive specific transcript (XIST)/miR-149-3p/forkhead box P3 (FOXP3) axis in ovarian cancer (OC) cell growth. XIST, miR-149-3p and FOXP3 expression in OC tissues and cell lines was assessed, and the predictive role of XIST in prognosis of OC patients was analyzed. The OC cell lines were screened and accordingly treated with silenced/overexpressed XIST plasmid or miR-149-3p mimic/inhibitor, and then the proliferation, invasion, migration, colony formation ability, apoptosis, and cell cycle distribution of OC cells were measured. Effect of altered XIST and miR-149-3p on tumor growth in vivo was observed. Online website prediction and dual luciferase reporter gene were implemented to detect the targeting relationship of lncRNA XIST, miR-149-3p, and FOXP3. XIST and FOXP3 were upregulated, whereas miR-149-3p was downregulated in OC tissues and cells. High XIST expression indicated a poor prognosis of OC. Inhibition of XIST or elevation of miR-149-3p repressed proliferation, invasion, migration, and colony formation ability, and promoted apoptosis and cell cycle arrest of HO-8910 cells. In SKOV3 cells upon treatment of overexpressed XIST or reduction of miR-149-3p, there exhibited an opposite tendency. Based on online website prediction, dual luciferase reporter gene, and RNA pull-down assays, we found that there was a negative relationship between XIST and miR-149-3p, and miR-149-3p downregulated FOXP3 expression. This study highlights that knockdown of XIST elevates miR-149-3p expression to suppress malignant behaviors of OC cells, thereby inhibiting OC development.

CNOT7 modulates biological functions of ovarian cancer cells via AKT signaling pathway

AimsCNOT7 plays an important role in many biological processes, providing attractive opportunities for the treatment of malignant tumors. However, the functions and mechanism of CNOT7 in ovarian cancer (OC) have not been elucidated. The purpose of this study was to assess the role of CNOT7 in OC. Materials and methodsSKOV3 and A2780 cells were chosen as the cell lines for the experiments of this manuscript via the analysis of the expression of CNOT7 protein and the mRNA level in ovarian surface epithelium (OSE) cells, SKOV3, HO8910 and A2780 cells. The expression of CNOT7 was detected by western blot assays and RT-PCR in A2780 and SKOV3 cells. The MTT assays, colony formation assays and EdU assays were used to measure cell proliferation when CNOT7 was knocked down or overexpressed in A2780 and SKOV3 cells. Furthermore, cell migration and invasion ability were achieved from transwell assays. Cell cycle and apoptosis rate after small interference RNA-CNOT7 (siRNA-CNOT7) were detected by flow cytometry assays. Finally, the cell proliferation, migration and invasion ability were detected when A2780 and SKOV3 cells with CNOT7 overexpression were treated with LY294002. Key findingsThe expression of CNOT7 protein in OC cells, including SKOV3, HO8910 and A2780 cells were significantly higher than that in OSE cells (P < 0.05). The mRNA level of CNOT7 in HO8910 and A2780 cells were significantly higher than that in OSE cells (P < 0.01). However, the mRNA level of CNOT7 in SKOV3 cells was no significant difference compared with OSE cells (P > 0.05). The results suggested that knockdown of CNOT7 could inhibit the cell proliferation, migration and invasion ability in A2780 and SKOV3 cells, and increase cell apoptosis and autophagy. The expression of apoptosis-related molecules (PARP, Caspase3 and Caspase9) and autophagy-related protein (LC3B) were up-regulated after CNOT7 knockdown, while the expression of cycle-related protein (CDK6) and the anti-apoptotic gene (Bcl2) were downregulated. Meanwhile, the opposite results were observed when CNOT7 was overexpressed in A2780 and SKOV3 cells. It is worth noting that the effect of CNOT7 overexpression in A2780 and SKOV3 cells could be partially or completely eliminated by treatment with AKT inhibitor LY294002. SignificanceCNOT7 has a carcinogenic effect in OC, and the carcinogenic effect may be achieved via the AKT signaling pathway.

Histone Methyltransferase KMT2D Regulates H3K4 Methylation and is Involved in the Pathogenesis of Ovarian Cancer

To investigate the function of histone-lysine N-methyltransferase 2D (KMT2D) on the methylation of H3 lysine 4 (H3K4) in the progression of Ovarian cancer (OV). KMT2D, ESR1 and H3K4me expressions in surgical resected tumors and tumor adjacent tissues of OV from 198 patients were determined using immunohistochemistry (IHC). Human OV cell lines including SKOV3, HO-8910 cells and normal ovarian epithelial cell line IOSE80 were employed for in vitro experiment, and BALB/C female nude mice were used for in vivo study. qRT-PCR and Western blotting were implemented for measuring the KMT2D, ESR1, PTGS2, STAT3, VEGFR2, H3K4me and ELF3 levels. Chromatin immunoprecipitation (ChIP) analysis was used for studying the binding between ESR1 and H3K4me. Edu staining assay was executed to determine cell viability, and colony formation and cell invasion assay. The immunofluorescence method was utilized for the visualization of protein expression and distribution in cells. In this study, KMT2D, ESR1 and H3K4me were found upregulated in OV progression. Mutated H3K4me could inhibit the proliferation, colony formation and invasion ability of OV cells. Mutated H3K4me could also hinder the ESR1 in SKOV3 expressions and HO-8910 cells, which would further mediate PTGS2/STAT3/VEGF pathway. In vivo studies also demonstrated that mutated H3K4me inhibited OV progression via targeting ESR1. All the ChIP-PCR analysis indicated the moderator effect of H3K4me on ESR1. Our findings indicated that ESR1 played an important role in the OV progression. Besides, H3K4me could promote cell proliferation and inhibit apoptosis of OV cells. Meanwhile, it could also targets the ESR1 production to enhance the migration and invasion of OV cells, which was through the activation of ESR1-ELF3-PTGS2-STAT3-VEGF cascade signaling pathway.

Dual inhibition of EGFR and IL-6-STAT3 signalling by miR-146b: a potential targeted therapy for epithelial ovarian cancer

Epidermal growth factor receptor (EGFR) signalling and the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) are aberrantly activated in ovarian cancer. However, inhibition of EGFR signalling in ovarian cancer patients resulted in a disappointing clinical benefit. In this study, we found that EGFR could activate IL-6-STAT3 pathway in ovarian cancer cells. However, we also demonstrated that EGFR knockdown could increase STAT3 phosphorylation in HO8910 and OVCAR-3 ovarian cancer cells. Interestingly, we further demonstrated that the non-coding RNA miR-146b could simultaneously block both the EGFR and IL-6-STAT3 pathways. Finally, our data demonstrated that miR-146b overexpression resulted in a greater suppression of cell migration than STAT3 pathway inhibition alone.These results suggest a complex and heterogeneous role of EGFR in ovarian cancer. Combined blockade of EGFR and IL-6-STAT3 pathways by miR-146b might be a strategy for improving the clinical benefit of targeting the EGFR pathway in ovarian cancer patients in the future.

Mechanism of resistin-induced enhancement of proliferation and migration of ovarian cancer cells

IntroductionResistin, a novel hormone secreted by human adipocytes and mononuclear cells, is associated with obesity, insulin resistance, and inflammation. Recent studies showed that resistin plays a key role in ovarian cancer cells. In this study, we investigated the potential of resistin to regulate the proliferation and migration of ovarian cancer cells.Material and methodsA series of in vitro functional experiments were carried out to elucidate the role of resistin in ovarian cancer progression and the molecular mechanisms underlying its role.ResultsResistin enhanced the proliferation of human ovarian epithelial carcinoma cells (HO-8910) in a time- and dose-dependent manner (30–100 ng/ml). Furthermore, HO-8910 cells cultured in adipocyte-conditioned medium showed dramatically increased rates of proliferation. Resistin knockout during adipocyte culture attenuated the proliferation of HO-8910 cells treated with adipocyte-conditioned media, indicating that resistin may promote HO-8910 cell proliferation via the mechanistic target of a rapamycin (mTOR)-mediated signaling pathway. Resistin (30–100 ng/ml) also enhanced wound-healing rates in a time- and concentration-dependent manner. Co-culturing HO-8910 cells with adipocytes also increased the wound-healing rates. Resistin expression was inhibited by miR-124-1 transcriptional activity, and resistin-mediated HO-8910 cell migration was also regulated by miR-124-1. Furthermore, we also confirmed the role of resistin in promoting tumor growth in vivo.ConclusionsThese findings suggest that resistin may serve as an effective therapeutic target for ovarian epithelial carcinoma, especially in patients who are obese.

Penicacids E-G, three new mycophenolic acid derivatives from the marine-derived fungus Penicillium parvum HDN17-478.

Three new mycophenolic acid derivatives, penicacids E-G (1-3), together with three known analogues, mycophenolic acid (4), 4'-hydroxy-mycophenolic acid (5) and mycophenolic methyl ester (6), were isolated from a marine-derived fungus Penicillium parvum HDN17-478 from a South China Sea marine sediment sample. The structures of compounds 1-3 were elucidated by HRMS, NMR, and Mosher's method. Among them, compounds 1 and 2 were the first examples of mycophenolic acid analogs with a double bond at C-3'/C-4' position. The cytotoxicity of 1-6 was evaluated against the HCT-116, BEL-7402, MGC-803, SH-SY5Y, HO-8910 and HL-60 cell lines, and compounds 4 and 6 showed potent cytotoxicity with IC50 values ranging from 1.69 to 12.98 μmol·L-1.

Ovarian cancer derived PKR1 positive exosomes promote angiogenesis by promoting migration and tube formation in vitro.

Cancer cell derived exosomes play important roles in cancer progression and modulation of the tumour microenvironment. This study aims to investigate the role of prokineticin receptor 1 (PKR1) positive exosomes on angiogenesis. In the present study, PKR1 expression in tumour samples from ovarian cancer patients were examined firstly. Then, two ovarian cancer cell lines, namely A2780 and HO-8910 cells, were used to isolate and obtain the PKR1 positive exosomes from the serum free medium. The function analysis of PKR1 positive exosomes on angiogenesis was conducted by cell proliferation and migration assay, tube formation analysis, and tumour volume assay. The results showed that PKR1 expression was down regulated in tumour samples of ovarian cancer patients compared with adjacent normal tissues. The intracellular expression of PKR1 could be detected in A2780 and HO-8910 cells. And, the isolated exosomes from the serum free medium were confirmed by transmission electron microscopic and NTA analysis, as well as the co-presence of PKR1 with exosome marker CD63. The function analysis of PKR1 positive exosomes on angiogenesis demonstrated the uptake of PKR1 positive exosomes by human umbilical vein endothelial cells through immunofluorescence staining. The angiogenesis assays in vitro indicated that PKR1 positive exosomes promoted migration and tube formation of HUVECs but not proliferation. The endogenous PKR1 was also verified to help to enhance migration and promote tube formation of vascular endothelial cells, which might involved in the phosphorylation of STAT3. Additionally, The tumour volume from exosomes treated A2780 tumour-bearing mice was significantly increased compared with the control group, accompanied with the induced PKR1 expression and phosphorylation of STAT3 level. SIGNIFICANCE OF THE STUDY: This study proved the important role of PKR1 positive exosomes released from ovarian cancer cells on promoting angiogenesis. The data indicated that PKR1 derived from ovarian cancer cells could act as an important tumour associated antigen and biomolecular factor for cellular communication in tumour microenvironment.

LAIR-1 suppresses cell growth of ovarian cancer cell via the PI3K-AKT-mTOR pathway.

Recently, over-expression of LAIR-1 has been found in some solid cancers, including ovarian cancer. The role of LAIR-1 in cancer progression needs further investigation. In this study, we identified the LAIR-1 cDNA sequence of the ovarian cancer cells HO8910. Using SKOV3 cells, we confirmed the finding from our previous study that LAIR-1 could suppress in vitro cell proliferation and cell migration. We also found LAIR-1 overexpression can induce apoptosis of SKOV3 cells. We revealed LAIR-1 suppressed cell growth by inhibiting the PI3K-AKT-mTOR axis. Moreover, the LAIR-1 antitumor activity and its mechanism were also identified in vivo. We used Co-IP assay and mass spectrometry to identify potential LAIR-1-binding proteins in LAIR-1 overexpressing SKOV3 cells. MS analysis identified 167 potentially interacting proteins. GO analyses indicated a possible involvement of LAIR-1 in mRNA processing through its interaction with some eukaryotic translation initiation factors (eIF4E1B, eIF2S3, eIF3D, eIF4G2, eIF5B) and eukaryotic translation elongation factors (eEF1A2 and eEF1B2). Our findings suggest that LAIR-1 may suppress the growth of ovarian cancer cells by serving as a modulator that suppresses PI3K-AKT-mTOR directly or regulating protein synthesis at the translational level. Our results indicate that a LAIR-1-based strategy may prevent or suppress the progression of ovarian cancer.

Cyclin H predicts the poor prognosis and promotes the proliferation of ovarian cancer

BackgroundCell cycle dysregulation plays a key role in the pathogenesis of malignant tumors. As a part of the CDK-activating kinase (CAK) trimeric complex, cyclin H is necessary to regulate the cell cycle and proliferation. This investigation aims to characterize the clinical significance and the biological functions of cyclin H in ovarian cancer.MethodsImmunohistochemical staining was performed on 60 ovarian cancer cases, and a correlation between cyclin H expression and the clinical characteristics of ovarian cancer was analyzed. The function of cyclin H in ovarian cancer was further explored using HO8910 cells and a subcutaneous xenograft model of nude mice.ResultCyclin H was slightly expressed in grade 1 ovarian cancer but highly expressed in grade 2 and grade 3 cancerous tissues. The Spearman’s rank correlation analysis showed that the expression of cyclin H is positively correlated with the tumor grade, the FIGO stage, histological grade, and the peritoneal metastasis of ovarian cancer and is also positively correlated with the Ki67 and p-CDK2 in ovarian cancer. Additionally, we found that the five-year survival rate was higher in patients expressing low cyclin H than those expressing high cyclin H. Further, knockdown of cyclin H was achieved using an shRNA in HO8910 ovarian cancer cell line. Silencing cyclin H resulted in a G1/S cell cycle arrest in ovarian cancer cells suppressing its growth. The Ki67 expression was also decreased in cyclin H silenced ovarian cancer.ConclusionThese results suggest that high expression of cyclin H predicts the poor prognosis and promotes the growth of ovarian cancer by regulating the cell cycle.

Purification, structural elucidation, and in vitro antitumor effects of novel polysaccharides from Bangia fuscopurpurea

A water-soluble polysaccharide, designated BFP-3, was isolated from Bangia fuscopurpurea by hot water extraction, anion-exchange, and size-exclusion chromatography and tested to determine its antitumor activity. The structural characteristics of BFP-3 were investigated by chemical and spectroscopic methods, including partial acid hydrolysis, methylation analysis, one- and two-dimensional nuclear magnetic resonance, and gas chromatography-mass spectrometry. The results showed that BFP-3 was mainly comprised of rhamnose, arabinose, mannose, glucose, and galactose. Moreover, the weight-average molecular weight of BFP-3 was estimated to be approximately 333 kDa. The backbone of BFP-3 was primarily composed of repeating 5-α-l-Araf-1→(4-α-d-Glcp-1)4→4,6-β-d-Manp-1 units, and the side chains consisted of repeating β-d-Galp-1→(4-β-d-Galp-1)4→4,6-β- d-Galp-1→3,4-α-l-Rhap, β-l-Arap-1→(3-β-d-Galp-1)3, and β-l-Arap-1 units. Counting Kit-8 assays revealed that BFP-3 significantly inhibited the proliferation of A2780, COC1, SKOV3, HO-8910, and OVCAR3 ovarian cancer cells in vitro, indicating that BFP-3 could have potential applications in the treatment of ovarian cancer.

Cytotoxic Meroterpenoids from the Fungus Alternaria sp. JJY-32.

Two new meroterpenoids, tricycloalternarenes X and Y, together with one known meroterpenoid, tricycloalternarene I, were isolated from the fungus Alternaria sp. JJY-32. The structures including absolute configurations were established by the comprehensive spectroscopic data, electronic circular dichroism (ECD) spectral analyses, and biosynthesis consideration. Tricycloalternarene X showed cytotoxicity against the HL-60 and HO8910 cells with IC50 values of 7.54 and 20.32 μm.

PNMA5 knockdown suppresses the proliferation, invasion, and metastasis of epithelial ovarian cancer cells.

BackgroundOvarian cancer is a severe gynecological malignancy. Paraneoplastic Ma antigen 5 (PNMA5) is a confirmed tumor onconeural antigen, which has been screened as a female fertility factor. PNMA5 overexpression might serve as a marker of poor prognosis in colon cancer. Our earlier study showed that PNMA5 was essential for meiosis in mouse oocytes. In this study, we investigate the role and probable mechanism of PNMA5 in the occurrence and development of epithelial ovarian cancer (EOC).MethodsImmunochemistry and western blot analyses were used to verify PNMA5 overexpression in clinical EOC tissues and EOC cell line HO8910. A specific siRNA was used to reduce PNMA5 levels, and several proliferation and migration-related indexes were assessed. We also examined mitochondria, microfilaments, and several essential kinases.ResultsWe found that the expression of PNMA5 in EOC tissues was significantly higher than that in benign ovarian tumors and healthy normal ovarian tissues and that this was strictly related to the FIGO stage and histological grade. PNMA5 expression in ovarian cancer cell line HO8910 was higher than that in the normal healthy ovarian cell line Moody. PNMA5 knockdown in HO8910 cells not only inhibited the proliferation, migration, invasion, cell cycle, and F-actin polymerization of HO8910 cells but also promoted early apoptosis and led to abnormal distribution and accumulation of mitochondria. PNMA5 phosphorylation was found to be positively regulated by Src activity, and PNMA5 phosphorylation promoted the downstream glycogen synthase kinase-3β (GSK-3β) signaling pathway.ConclusionsPNMA5 plays a pivotal role in the occurrence and development of EOC and is a potential marker of this disease.

Smad4 induces cell death in HO-8910 and SKOV3 ovarian carcinoma cell lines via PI3K-mTOR involvement.

This study investigated the effect and mechanism of Smad4 in ovarian carcinoma (OC) cell viability and demonstrated that Smad4 acted as a tumor suppressor in OC, which may contribute to the understanding of molecular mechanisms underlying OC occurrence and progression. Smad4 expression was decreased in the OC specimens, but Smad4 recovery in the OC cell lines impaired the survival and viability of OC cells by increasing autophagy and apoptosis. Further investigation showed that Smad4 interacted with the P85 subunit of PI3K and caused deactivation of the PI3K/mTOR pathway. Therefore, Smad4 could be considered as a target in cancer therapy due to its regulatory effect in OC carcinogenesis.

Examination of the relationship between viscoelastic properties and the invasion of ovarian cancer cells by atomic force microscopy.

The mechanical properties of cells could serve as an indicator for disease progression and early cancer diagnosis. This study utilized atomic force microscopy (AFM) to measure the viscoelastic properties of ovarian cancer cells and then examined the association with the invasion of ovarian cancer at the level of living single cells. Elasticity and viscosity of the ovarian cancer cells OVCAR-3 and HO-8910 are significantly lower than those of the human ovarian surface epithelial cell (HOSEpiC) control. Further examination found a dramatic increase of migration/invasion and an obvious decease of microfilament density in OVCAR-3 and HO-8910 cells. Also, there was a significant relationship between viscoelastic and biological properties among these cells. In addition, the elasticity was significantly increased in OVCAR-3 and HO-8910 cells after the treatment with the anticancer compound echinomycin (Ech), while no obvious change was found in HOSEpiC cells after Ech treatment. Interestingly, Ech seemed to have no effect on the viscosity of the cells. Ech significantly inhibited the migration/invasion and significantly increased the microfilament density in OVCAR-3 and HO-8910 cells, which was significantly related with the elasticity of the cells. An increase of elasticity and a decrease of invasion were found in OVCAR-3 and HO-8910 cells after Ech treatment. Together, this study clearly demonstrated the association of viscoelastic properties with the invasion of ovarian cancer cells and shed a light on the biomechanical changes for early diagnosis of tumor transformation and progression at single-cell level.

LINC00460 accelerates progression of ovarian cancer by activating transcriptional factor ZNF703.

Potential function of LINC00460 in the progression of ovarian cancer (OC) and its underlying mechanism were studied. LINC00460 level in OC tissues and normal ovarian tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between LINC00460 level with tumor stage, tumor size and pathological subtypes of OC was analyzed. Potential influence of LINC00460 on proliferative ability and cell cycle progression was evaluated. In vivo tumorigenesis model was conducted by administration of A2780 cells transfected with sh-NC or sh-LINC00460 in nude mice. Predicted through JASPAR database, ZNF703 was screened out as the transcriptional factor binding to LINC00460 promoter region. Chromatin immunoprecipitation (ChIP) assay was performed to verify the binding relationship between ZNF703 and LINC00460. The potential role of ZNF703 in LINC00460-mediated OC progression was examined. LINC00460 was upregulated in OC tissues and cell lines. Its level increased with the deterioration of tumor stage and enlargement of tumor size. LINC00460 was highly expressed in serous ovarian cancer relative to other subtypes of OC. Knockdown of LINC00460 attenuated proliferative ability and arrested cell cycle of A2780 and HO8910 cells. ZNF703 was upregulated in OC tissues. ChIP assay showed pronounced enrichment of LINC00460 in ZNF703. Rescue experiments revealed that ZNF703 overexpression reversed the regulatory effects of LINC00460 on cellular behavior of OC cells. LINC00460 is upregulated in OC tissues and cell lines, which is closely related to tumor progression. It accelerates proliferative ability and cell cycle progression of OC cells via interacting with ZNF703.

LncRNA MIF-AS1 aggravates the progression of ovarian cancer by sponging miRNA-31-5p.

The aim of this study was to uncover the role of lncRNA MIF-AS1 in influencing the biological phenotypes of ovarian cancer (OC) and the underlying mechanism. OC tissues and adjacent normal tissues were collected from 50 OC patients. The expression level of lncRNA MIF-AS1 in OC tissues and cells was determined by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The prognostic potential of MIF-AS1 in OC patients was assessed by the Kaplan-Meier method. Subsequently, the regulatory effects of MIF-AS1 on proliferative, migratory, and invasive abilities of ES-2 and HO-8910 cells were evaluated by a series of functional experiments. Dual-Luciferase reporter gene assay, qRT-PCR, and Western blot were further conducted to verify the interaction in the regulatory loop MIF-AS1/miRNA-31-5p/PLCB1. MIF-AS1 was significantly upregulated in OC tissues and cell lines (p<0.05). Higher level of MIF-AS1 predicted significantly worse prognosis of OC patients (p<0.05). The knockdown of MIF-AS1 markedly attenuated the proliferative, migratory, and invasive abilities of ES-2 and HO-8910 cells (p<0.05). Dual-Luciferase reporter gene assay verified that MIF-AS1 competed with PLCB1 to bind miRNA-31-5p. In addition, MIF-AS1 negatively regulated miRNA-31-5p expression cells, and miRNA-31-5p negatively regulated PLCB1 expression in OC. MIF-AS1 was significantly upregulated in OC, which accelerated the proliferative, migratory, and invasive abilities of OC cells. Furthermore, the regulatory loop MIF-AS1/miRNA-31-5p/PLCB1 could be utilized as a therapeutic target for OC.

The Impact of Paclitaxel-Containing Nanoliposomes on the Proliferation of and Invasion by Ovarian Cancer Cells

Our goal was to explore the impact of paclitaxel-containing nanoliposomes (PTXN) on the proliferation of and invasion by ovarian carcinoma cells. An MTT assay was used to examine growth of SKOV3 and HO8910 ovarian carcinoma cells in the presence of paclitaxel (TAX) alone or PTXN. Transwell invasion assays were performed; Western blot and qRT-PCR were used to examine expression of matrix metallopeptidase (MMP)-9. PTXN administered at concentrations from 0.625–10 μg/mL was more effective at inhibiting the proliferation of SKOV3 and HO8910 cells than was TAX alone (P &lt; 0.05). Administration of PTXN to these cells reduced their capacity for invasion, and expression of MMP-9 mRNA and protein over that achieved by administration of TAX alone (P &lt; 0.05). PTXN promotes more effective inhibition of invasion of ovarian carcinoma cells than does TAX alone.

Linc-UBC1 stimulates the metastasis and progression of ovarian cancer via downregulating p53 level.

To elucidate the role of linc-UBC1 in regulating the metastasis and progression of ovarian cancer (OC) by downregulating the p53 level. Relative levels of linc-UBC1 in OC tissues and paracancerous tissues were determined by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Differential expressions of linc-UBC1 in OC tissues with different tumor staging or tumor sizes were detected as well. Receiver operating characteristic (ROC) curves were introduced for assessing the diagnostic value of linc-UBC1 in OC. After silence of linc-UBC1, proliferative and migratory abilities of HO8910 and HEY cells were evaluated. Subcellular distribution of linc-UBC1 was analyzed. The interaction between linc-UBC1 and p53 was explored through the RNA immunoprecipitation (RIP) assay. At last, rescue experiments were conducted to uncover the role of linc-UBC1/p53 regulatory loop in influencing the progression of OC. Linc-UBC1 was upregulated in OC and its level negatively correlated to that of p53. Linc-UBC1 level was higher in OC patients with advanced TNM staging or larger tumor size. Linc-UBC1 was mainly distributed in the nucleus. Silence of linc-UBC1 attenuated proliferative and migratory abilities of HO8910 and HEY cells. RIP assay verified that linc-UBC1 could inhibit the transcription of p53. Knockdown of p53 could partially reverse the regulatory effects of linc-UBC1 on regulating the progression of OC. Linc-UBC1 is upregulated in OC tissues and cells. It stimulates the proliferation and metastasis of OC by downregulating p53 level, thus exerting a carcinogenic role.

Regulatory mechanism of lncRNA NORAD on proliferation and invasion of ovarian cancer cells through miR-199a-3p.

To explore the regulatory mechanism of lncRNA NORAD on proliferation and invasion of ovarian cancer cells through miR-199a-3p. Eighty-six ovarian cancer tissues and 86 tissues adjacent to cancer, human ovarian cancer cell lines SKOV3, HO-8910, A2780, OVCAR-3, and human normal ovarian epithelial cell line IOSE80 were collected. MiR-199a-3p-mimics, miR-199a-3p-inhibitor, miR-NC, si-NORAD, Sh-NORAD, and NC were transfected into HO-8910 and A2780 cells, the expression levels of lncRNA NORAD and miR-199a-3p in ovarian cancer tissues and cells were detected by qRT-PCR, and the expression levels of N-cadherin, E-cadherin, and vimentin in cells were detected by WB. Cell Counting Kit-8 (CCK-8), transwell, and cell scratch tests were used to detect proliferation, invasion, and migration of cells, and the relationship between lncRNA NORAD and miR-199a-3p was confirmed by the Dual-Luciferase reporter assay. LncRNA NORAD was highly expressed and miR-199a-3p was lowly expressed in ovarian cancer, and the expression levels of LNCRNARAD and miR-199a-3p were negatively correlated. Cell experiments showed that inhibiting the expression of lncRNA NORAD or up-regulating the expression of miR-199a-3p could inhibit the proliferation, invasion, migration, and EMT of ovarian cancer cells, while up-regulating the expression of lncRNA NORAD or inhibiting the expression of miR-199a-3p could promote their proliferation, invasion, migration, and EMT. Dual-Luciferase reporter assay confirmed that there was a regulatory relationship between lncRNA NORAD and miR-199a-3p. LncRNA NORAD was highly expressed in ovarian cancer tissues, while silencing lncRNA NORAD expression could inhibit the proliferation, invasion, migration, and EMT of ovarian cancer cells by regulating miR-199a-3p, which might be a new target for the diagnosis and treatment of ovarian cancer.