High expression of NQO1 is associated with poor prognosis in serous ovarian carcinoma

Cui, Xia; Li, Lianhua; Yan, Guanghai; Meng, Kai; Lin, Zhenhua; Nan, Yunze; Jin, Guang; Li, Chunyu

doi:10.1186/s12885-015-1271-4

Cited by 61 publications

(52 citation statements)

References 34 publications

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“…NQO1 is generally recognized as a 'cell protector', its induction in response to various noxious stimuli provides protection for cells against oxidative damage and oxidative stress-associated pathological conditions including cancer (9,10). Conversely, an increasing number of studies revealed abnormal increases in NQO1 expression levels in solid tumors of the adrenal gland, breast, colon, lung, ovary, pancreas, thyroid, skin and bladder (9)(10)(11)(12)(13)(14)(15)(16). High-level expression of NQO1 may be associated with cancer progression and it was suggested to be a poor prognostic marker of these types of cancer (14,16,17).…”

Section: Introductionmentioning

confidence: 99%

“…Conversely, an increasing number of studies revealed abnormal increases in NQO1 expression levels in solid tumors of the adrenal gland, breast, colon, lung, ovary, pancreas, thyroid, skin and bladder (9)(10)(11)(12)(13)(14)(15)(16). High-level expression of NQO1 may be associated with cancer progression and it was suggested to be a poor prognostic marker of these types of cancer (14,16,17). Upregulation of NQO1 during carcinogenesis may provide cancer cells with a growth advantage and protection against extreme oxidative stress environments (10,11).…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of NAD(P)H:quinone oxidoreductase 1 inhibits proliferation, cell cycle and migration of cholangiocarcinoma cells

et al. 2017

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Abstract. We previously reported that upregulation of NAD(P)H:quinone oxidoreductase 1 (NQO1) in cholangiocarcinoma (CCA; a fatal bile duct cancer) was associated with poor prognosis. It was also demonstrated that the suppression of NQO1 was able to enhance the chemosensitivity of CCA cells. In the present study, in order to elucidate the biological role of NQO1 in CCA, the effects of small interfering RNA (siRNA)-mediated knockdown of NQO1 on cell proliferation, cell cycle and migration were determined in KKU-100 CCA cells, which notably expressed NQO1. The cell proliferation ability and cell cycle distribution were identified by clonogenic cell survival assay and flow cytometric analysis, respectively. Wound healing and Transwell migration assays were performed to evaluate cell migration. The molecules involved in cell proliferation and migration were determined by western blot analysis and reverse transcription-quantitative polymerase chain reaction analysis. The results demonstrated that NQO1 siRNA-mediated knockdown effectively impaired colony formation capacity, induced cell cycle arrest at the G 1 phase and suppressed migration of KKU-100 cells. CCA cells transfected with NQO1 siRNA exhibited increased expression levels of p21 and decreased cyclin D1 protein expression levels. Furthermore, the ratio of matrix metalloproteinase 9/tissue inhibitors of metalloproteinases 1 (TIMP1) mRNA expression level was decreased in the NQO1-knockdown cells. Therefore, the present study provided evidence supporting the biological role of NQO1 in the regulation of cell proliferation, cell cycle and migration of CCA cells. Therefore, NQO1 may prove to be a potential molecular target to enhance CCA treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Downregulation of NAD(P)H:quinone oxidoreductase 1 inhibits proliferation, cell cycle and migration of cholangiocarcinoma cells

et al. 2017

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“…PV9000; ZSGB-Bio, Beijing, China) at RT for 30 min, the slides were incubated with streptavidin-peroxidase complex at RT for 30 min. Immunostaining was developed using 3,3'-diaminobenzidine, and Mayer's hematoxylin was used for counterstaining (20). Rabbit immunoglobulin G (IgG) (1:2,500 dilution; catalog no.…”

Section: Methodsmentioning

confidence: 99%

Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma

Cui

Chen

et al. 2016

Oncology Letters

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Abstract. T lymphoma invasion and metastasis 1 (Tiam1), a guanine nucleotide exchange factor, was originally identified as an invasion-and metastasis-inducing gene in T lymphoma cells. High expression levels of the human Tiam1 gene have been found in numerous human malignancies, suggesting a potential role as a modifier of tumor initiation and progression. However, little is known about the status of Tiam1 in ovarian carcinoma. The present study aimed to investigate the clinicopathological significance of high Tiam1 expression in serous ovarian carcinoma. Immunohistochemical staining for Tiam1 was performed in 182 patients with serous ovarian carcinoma, in 76 patients with ovarian borderline tumors and in 72 patients with benign ovarian tumors. Immunofluorescence staining was also performed to detect the subcellular localization of Tiam1 protein in SK-OV-3 ovarian carcinoma cells. The correlations between high Tiam1 expression and the clinicopathological features of the ovarian carcinomas were evaluated by the χ 2 test and Fisher's exact test. The overall survival (OS) rates were calculated by the Kaplan-Meier method, and the association between prognostic factors and patient survival was analyzed by the Cox proportional hazard model. Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma. Strongly-positive Tiam1 protein expression was observed in 59.3% (108/182) of ovarian carcinomas, which was significantly higher than in benign serous tumors (12.5%; 9/72). Moreover, the rate of strongly-positive Tiam1 expression in borderline serous tumors (31.6%; 24/76) was also significantly higher than that in benign serous tumors. High Tiam1 protein expression was closely associated with a high histological grade, metastasis, advanced clinical stage and lower OS rates in ovarian carcinoma. Multivariate analysis indicated that Tiam1 was an independent prognostic factor, along with metastasis and clinical stage, in patients with ovarian carcinoma. In conclusion, Tiam1 expression is strongly associated with grade and outcome in ovarian carcinoma, and may serve as a useful molecular marker for clinical management.

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“…Interestingly, a predicted target of the under-expressed miR-148, NQO1 gene, was found to have a large number of interactions and to be up-regulated in CCA. NQO1 over-expression occurs in different tumors compared to their normal surrounding tissues [62] and was recently associated with poor prognosis in serous ovarian cancer [63]. Cholangiocarcinoma is highly resistant to chemotherapy and NQO1 protein, NAD(P)H-quinone oxidoreductase 1, has been shown to play a cooperative role in cancer chemoresistance [64].…”

Section: Figurementioning

confidence: 99%

Integrative Analysis of Transcriptome and MicroRNome Profiles in Cholangiocarcinoma

Severino¹,

Hasimoto²,

Rodrigues³

et al. 2017

J Cancer Sci Ther

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Aim: To identify deregulated expression of miRNAs and target genes in cholangiocarcinoma (CCA), as well as drug-gene interactions that may be useful for patient treatment. Methods:We analyzed quantitative transcriptome and miRNA deep sequencing expression data from 45 samples, 36 CCA and 9 histologically normal biliary tissues, obtained from the public repository The Cancer Genome Atlas (TCGA). Bioinformatic methods were used to identify and integrate differential expression of miRNA and transcriptome profiles in CCA vs. normal tissues. Deregulated miRNA and corresponding target genes were identified and mapped into miRNA-mRNA networks. Results:Results showed 64 differentially expressed miRNAs (48 over and 16 under-expressed) between CCA and corresponding normal biliary tissues. Additionally, 432 genes (180 over and 252 under-expressed) were identified between CCA and normal samples. We identified individual miRNAs with the largest number of gene targets. Among these, miR-125a was over-expressed and had the highest number of direct interactions with 33 mRNA targets. miRNAs miR-122 and miR-139 were the under-expressed miRNAs with the highest number of interactions (9 targets each). miR-122 was found to modulate the expression of the transcription factor FOXM1, known to be involved in tumorigenesis and the matrix metalloproteinase MMP7, an important mediator of tumor invasion. miR-148 and miR-194 were predicted to modulate NQO1, which is up-regulated in cancer and associated with treatment resistance in cholangiocarcinoma. Conclusion:The novelty of our study is the identification of complex deregulated networks of miRNAs and target genes in CCA. miRNAs with a large number of targets may have a higher functional impact on cell regulation. These findings contribute for a better understanding of CCA biology. Identified miRNAs and target genes are potential candidates for the design of validation strategies towards the characterization of clinically applicable biomarkers; such biomarkers may be useful for the development of molecularly-targeted therapeutics that can benefit patients.

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High expression of NQO1 is associated with poor prognosis in serous ovarian carcinoma

Cited by 61 publications

References 34 publications

Downregulation of NAD(P)H:quinone oxidoreductase 1 inhibits proliferation, cell cycle and migration of cholangiocarcinoma cells

Downregulation of NAD(P)H:quinone oxidoreductase 1 inhibits proliferation, cell cycle and migration of cholangiocarcinoma cells

Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma

Integrative Analysis of Transcriptome and MicroRNome Profiles in Cholangiocarcinoma

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