MicroRNAs in ovarian carcinomas

Dahiya, Neetu; Morin, Patrice J.

doi:10.1677/erc-09-0203

Cited by 100 publications

(111 citation statements)

References 92 publications

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“…miRs, a class of gene regulators, have been proven to be effective in classifying normal and cancerous tissues as well as cancer prognosis. Data on ovarian cancer thus far indicate that the miR network is very important to understanding ovarian cancer biology and resistance to therapy (19,20). Analyzing 198 samples of serous ovarian carcinoma, we discovered that three miRs (484, 642, and 217) were capable of conferring a responder or nonresponder status on ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis

Vecchione

Belletti

Lovat

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

176

133

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Epithelial ovarian cancer is the most lethal gynecologic malignancy; it is highly aggressive and causes almost 125,000 deaths yearly. Despite advances in detection and cytotoxic therapies, a low percentage of patients with advanced stage disease survive 5 y after the initial diagnosis. The high mortality of this disease is mainly caused by resistance to the available therapies. Here, we profiled microRNA (miR) expression in serous epithelial ovarian carcinomas to assess the possibility of a miR signature associated with chemoresistance. We analyzed tumor samples from 198 patients (86 patients as a training set and 112 patients as a validation set) for human miRs. A signature of 23 miRs associated with chemoresistance was generated by array analysis in the training set. Quantitative RT-PCR in the validation set confirmed that three miRs (miR-484, -642, and -217) were able to predict chemoresistance of these tumors. Additional analysis of miR-484 revealed that the sensitive phenotype is caused by a modulation of tumor vasculature through the regulation of the VEGFB and VEGFR2 pathways. We present compelling evidence that three miRs can classify the response to chemotherapy of ovarian cancer patients in a large multicenter cohort and that one of these three miRs is involved in the control of tumor angiogenesis, indicating an option in the treatment of these patients. Our results suggest, in fact, that blockage of VEGF through the use of an anti-VEGFA antibody may not be sufficient to improve survival in ovarian cancer patients unless VEGFB signaling is also blocked.

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Section: Discussionmentioning

confidence: 99%

A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis

Vecchione

Belletti

Lovat

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

176

133

View full text Add to dashboard Cite

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“…Although the majority of ovarian cancer patients will respond to initial chemotherapy, most will ultimately develop disease recurrence (12). To develop more optimized and effective treatment strategies for ovarian cancer, it is critical to gain a deeper understanding of the molecular mechanisms of ovarian cancer and to identify targets for therapeutic intervention (13)(14)(15)(16). MiRNAs have recently been described as important players in human cancer and the role of microRNA as therapeutic targets has been proposed (17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer

Zhang

Zuo²,

Lü³

et al. 2011

Oncol Rep

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Abstract. MicroRNAs (miRNAs) are emerging as a class of small regulatory RNAs whose alterations are implicated in the initiation and progression of human cancers. Our study showed that miR-25 was highly expressed both in clinical ovarian cancer samples and cell lines. Down-regulation of miR-25 in ovarian cancer cells induced apoptosis whereas overexpression of miR-25 enhanced cell proliferation. The effects of miR-25 abrogation were partly mediated by the intrinsic apoptosis pathway. Many pro-apoptotic proteins such as Bim, Bax and caspase-3 were up-regulated after transfection. Furthermore, luciferase assays demonstrated that Bim was the direct target of miR-25. Introducing Bim cDNA without 3'UTR abrogated miR-25-induced cell survival. Finally, there was an inverse relationship between Bim and miR-25 expression in ovarian cancer tissues. Taken together, these data indicate that miR-25 directly regulates apoptosis by targeting Bim in ovarian cancer and that miR-25 could be a potential therapeutic target for ovarian cancer intervention.

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“…However, there is no documentation on the protein level that could be affected by siRNA and possibly by various intracellular proteinases (reviewed in refs. [52][53][54]. Moreover, high percentage of normal ovaries defined by straight morphology were found by us as already at the stage of benign or even borderline tumors.…”

Section: Discussionmentioning

confidence: 56%

Epiregulin as a marker for the initial steps of ovarian cancer development

Amsterdam

Shezen²,

Raanan³

et al. 2011

Int J Oncol

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Abstract. Epiregulin (Ep) was found to be produced in noncancer ovarian cells in response to gonadotropin stimulation as well in ovarian cancer cells in an autonomous manner. However, there were no systematic follow-up studies of Ep expression in the development of different stages of ovarian cancer. Using specific antibodies to Ep and the indirect immunocytochemistry methods, we found that in normal ovary the staining for Ep was mainly confined to the epithelial cells, while the stromal cells were only occasionally and moderately stained. In contrast in benign serous and mucinous tumors most of the tumor cells showed a clear staining in the cytoplasm. In borderline serous and mucinous tumors the staining was much more intensive, and appear occasionally in aggregated form. In serous, mucinous and endometrioid carcinomas labeling remain high, with more frequent aggregated form. It is suggested that follow-up of the expression of Ep can serve as a reliable early indication of the development of ovarian cancer. Moreover, the cytoplasmic aggregation of Ep may suggest a specific mechanism of the release of this growth factor to the extracellular space in order to exert its autocrine and paracrine effect on the family of the EGF receptors.

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MicroRNAs in ovarian carcinomas

Abstract: The molecular mechanisms involved in epithelial ovarian cancer initiation and progression are

Cited by 100 publications

References 92 publications

A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis

A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis

MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer

Epiregulin as a marker for the initial steps of ovarian cancer development

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