scholarly journals Comprehensive analysis of mRNA‐level and miRNA‐level subpathway activities for identifying robust ovarian cancer prognostic signatures

2020 ◽  
Vol 24 (4) ◽  
pp. 2582-2592
Author(s):  
Songyu Tian ◽  
Wanqi Mi ◽  
Mingyue Zhang ◽  
Linan Xing ◽  
Chunlong Zhang
2021 ◽  
Vol 10 (14) ◽  
pp. 3058
Author(s):  
Aleksandra Mielczarek-Palacz ◽  
Celina Kruszniewska-Rajs ◽  
Marta Smycz-Kubańska ◽  
Jarosław Strzelczyk ◽  
Wojciech Szanecki ◽  
...  

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research.


Medicine ◽  
2020 ◽  
Vol 99 (47) ◽  
pp. e22777
Author(s):  
Hong-Yu Xu ◽  
Hua-Mei Song ◽  
Quan Zhou

2018 ◽  
Author(s):  
Felipe Vaca-Paniagua ◽  
Rosalía Quezada-Urban ◽  
Clara E. Díaz-Velásquez ◽  
Rina Gitler ◽  
María P. Rojo-Castillo ◽  
...  

2019 ◽  
Author(s):  
Felipe Vaca-Paniagua ◽  
Rosalia Quezada-Urban ◽  
Clara Estela Díaz Velásquez ◽  
Eva María Gómez García ◽  
Claudia Fabiola Méndez Catalá ◽  
...  

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruth M. Escalona ◽  
Maree Bilandzic ◽  
Patrick Western ◽  
Elif Kadife ◽  
George Kannourakis ◽  
...  

Abstract Background The metzincin family of metalloproteinases and the tissue inhibitors of metalloproteinases (TIMPs) are essential proteins required for biological processes during cancer progression. This study aimed to determine the role of TIMP-2 in ovarian cancer progression and chemoresistance by reducing TIMP-2 expression in vitro in Fallopian tube secretory epithelial (FT282) and ovarian cancer (JHOS2 and OVCAR4) cell lines. Methods FT282, JHOS2 and OVCAR4 cells were transiently transfected with either single or pooled TIMP-2 siRNAs. The expression of different genes after TIMP-2 knock down (T2-KD) or in response to chemotherapy was determined at the mRNA level by quantitative real time PCR (qRT-PCR) and at the protein level by immunofluorescence. Sensitivity of the cell lines in response to chemotherapy after TIMP-2 knock down was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-Ethynyl-2′-deoxyuridine (EdU) assays. Cell invasion in response to TIMP-2 knockdown was determined by xCELLigence. Results Sixty to 90 % knock down of TIMP-2 expression was confirmed in FT282, OVCAR4 and JHOS2 cell lines at the mRNA and protein levels. TIMP-2 knock down did not change the mRNA expression of TIMP-1 or TIMP-3. However, a significant downregulation of MMP-2 in T2-KD cells occurred at both the protein and activation levels, compared to Control (Cont; scrambled siRNA) and Parental cells (P, transfection reagent only). In contrast, membrane bound MT1-MMP protein levels were significantly upregulated in T2-KD compared to Cont and P cells. T2-KD cells exhibited enhanced proliferation and increased sensitivity to cisplatin and paclitaxel treatments. Enhanced invasion was observed in the T2-KD-JOSH2 and OVCAR4 cells but not in T2-KD-FT282 cells. Treatment with cisplatin or paclitaxel significantly elevated the expression of TIMP-2 in Cont cells but not in T2-KD cells, consistent with significantly elevated expression of chemoresistance and CSC markers and activation of STAT3. Furthermore, a potent inhibitor of STAT3 activation, Momelotinib, suppressed chemotherapy-induced activation of P-STAT3 in OVCAR4 cells with concomitant reductions in the expression of chemoresistance genes and CSC markers. Conclusions The above results suggest that TIMP-2 may have a novel role in ovarian cancer proliferation, invasion and chemoresistance.


2004 ◽  
Vol 22 (4) ◽  
pp. 678-685 ◽  
Author(s):  
Andreas Scorilas ◽  
Carla A. Borgoño ◽  
Nadia Harbeck ◽  
Julia Dorn ◽  
Barbara Schmalfeldt ◽  
...  

PurposeHuman kallikrein 13 (hK13; encoded by the KLK13 gene) is a secreted serine protease expressed in endocrine tissues, including the prostate, testis, breast, and ovary. We have previously reported steroid hormone regulation of the KLK13 gene and its clinical value as a marker of favorable prognosis in breast cancer at the mRNA level. We hypothesized that hK13 may represent a potential biomarker for ovarian carcinomas.Patients and MethodsUsing a newly developed enzyme-linked immunosorbent assay (ELISA), hK13 levels were quantified in 131 ovarian tumor extracts and correlated with various clinicopathological variables and outcome (progression-free survival [PFS], overall survival [OS]), over a median follow-up period of 42 months.ResultshK13 concentration in ovarian tumor cytosols ranged from 0 to 18.4 ng/mg of total protein. An optimal cutoff value of 0.13 ng/mg (67thpercentile) was selected, based on the ability of hK13 values to predict the PFS of the study population, to categorize tumors as hK13-positive or negative. Women with hK13-positive tumors most often had early stage (stage I/II) disease, no residual tumor after surgery and optimal debulking success (P < .05). Univariate and multivariate Cox regression analyses revealed that patients with hK13-positive tumors had a significantly longer PFS and OS than hK13-negative patients (P < .05). Kaplan-Meier survival curves further confirmed a reduced risk of relapse and death in women with hK13-positive tumors (P = .007 and P = .002, respectively).ConclusionThese results indicate that hK13 is an independent marker of favorable prognosis in ovarian cancer.


PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80306 ◽  
Author(s):  
Rozita Akrami ◽  
Anders Jacobsen ◽  
Jessica Hoell ◽  
Nikolaus Schultz ◽  
Chris Sander ◽  
...  

2008 ◽  
Vol 389 (11) ◽  
Author(s):  
Hellinida Thomadaki ◽  
Andreas Scorilas

Abstract We assessed changes in the apoptosis-related genes BCL2, BAX, BCL2L12, FAS and CASPASE-3 in OVCAR-3 human ovarian cancer cells and BT-20 human breast cancer cells to provide an insight into the molecular mechanisms involved in the response of these cells to treatment with anticancer drugs and to assess their value as potential biomarkers of chemotherapy response in breast and ovarian cancer. Cells were treated with different chemotherapeutic drugs (cisplatin, carboplatin, doxorubicin, etoposide and taxol) and assessed for changes in the expression of apoptosis-related genes at the mRNA level. Total RNA was extracted, reverse-transcribed into cDNA and amplified by PCR using gene-specific primers. GAPDH was used as a housekeeping gene. Cytotoxicity was assessed by MTT assay. Both cancer cell lines responded differentially at the molecular level to the drug treatments. OVCAR-3 cells showed more pronounced sensitivity and changes compared to BT-20 cells at the mRNA level for different apoptosis-related genes, leading to cell and cancer type dependence in conjunction with drug dependence.


2016 ◽  
Vol 38 (5) ◽  
pp. 1915-1927 ◽  
Author(s):  
Peiquan Li ◽  
Yuxin Sun ◽  
Qing Liu

Aims: Aberrant expression of microRNA-340 (miR-340) has been frequently reported in some cancers excluding ovarian cancer (OC). The role and its molecular mechanism of miR-340 in OC have not been reported. Methods: Real-time PCR was performed to detect the expression of miR-340 in OC cell lines. MiR-340 mimic and negative control were transfected into OC cells and the effects of miR-340 on the cell proliferation, cell cycle, apoptosis and metastasis were investigated by Brdu-ELISA assay, flow cytometry, qRT-PCR, Transwell and ELISA assays. Furthermore, protein level of NF-κB1 was measured by Western blotting. Meanwhile, luciferase assays were performed to validate NF-κB1 as miR-340 target in OC cells. Results: In this study, we explored the effects of miR-340 overexpression on apoptosis, invasion and EMT in OC cells. The mRNA level of miR-340 in OC cell lines and tissues was evidently reduced. The miR-340 mimic was transiently transfected into OC cells using Lipofectamine™ 2000 reagent. Subsequently, the Brdu-ELISA results showed that introduction of miR-340 inhibited cell proliferation. Our data also demonstrated that miR-340 mimic arrested cell cycle progression and promoted apoptosis of OC cells. In addition, miR-340 overexpression could also inhibit invasion and EMT of OC cells. qRT-PCR were used to determined the expressions of matrix metalloproteinase-2 and -9 (MMP-2 and -9) in OC cells. Next, we found that NF-κB1 expression was evidently reduced by up-regulation of miR-340. Bioinformatics analysis predicted that the NF-κB1 was a potential target gene of miR-340. Luciferase reporter assay further confirmed that miR-340 could directly target the 3' UTR of NF-κB1. Moreover, overexpression of NF-κB1 in OC cells transfected with miR-340 mimic partially reversed the inhibitory of miR-340 mimic. Conclusion: miR-340 induced cell apoptosis and inhibited metastasis in OC cells by down-regulation of NF-κB1.


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