Background: MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease.

Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line. The platelet antagonists [cangrelor, MRS2179, and apyrase] inhibited 59M cell induced activation suggesting a P2Y12 and P2Y1 receptor mediated mechanism of platelet activation dependent on the release of ADP by 59M cells. A2780 and 59M cells potentiated PAR-1, PAR-4, and TxA2 receptor mediated platelet activation, but had no effect on ADP, epinephrine, or collagen induced activation. Analysis of gene expression changes in ovarian cancer cells following treatment with washed platelets or platelet releasate showed a subtle but valid upregulation of anti-apoptotic, anti-autophagy pro-angiogenic, pro-cell cycle and metabolic genes. Thus, ovarian cancer cells with different metastatic potential adhere and activate platelets differentially while both platelets and platelet releasate mediate pro-survival and pro-angiogenic signals in ovarian cancer cells.

MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. Production and function of microRNAs require coordinated processing by proteins of the microRNA machinery. Dicer and Drosha (RNase III endonucleases) are essential components of the microRNA machinery. Recently, the ribosome anti-association factor eIF6 has also been found to have a role in microRNA-mediated post-transcriptional silencing. We characterized the alterations in the expression of genes encoding proteins of microRNA machinery in ovarian serous carcinoma. Protein expression of eIF6 and Dicer was quantified in a tissue microarray of 66 ovarian serous carcinomas. Dicer, Drosha and eIF6 mRNA expression was analysed using quantitative reverse transcription-PCR on an independent set of 50 formalin-fixed, paraffin-embedded ovarian serous carcinoma samples. Expression profiles of eIF6 and Dicer were correlated with clinicopathological and patient survival data. We provide definitive evidence that eIF6 and Dicer are both upregulated in a significant proportion of ovarian serous carcinomas and are associated with specific clinicopathological features, most notably low eIF6 expression being associated with reduced disease-free survival. The status of eIF6 and proteins of the microRNA machinery may help predict toxicity and susceptibility to future interfering RNA-based therapy.

BackgroundPelvic irradiation is essential for improving survival in women with pelvic malignancies despite inducing permanent ovarian damage. Ovarian transposition can be performed in premenopausal women in an attempt to preserve ovarian function. As uncertainty occurs over the proportion of women who are likely to benefit from the procedure, we performed a systematic review and meta-analysis of the proportion of women with ovarian function preservation, symptomatic or asymptomatic ovarian cysts and metastatic ovarian malignancy following ovarian transposition.MethodsMedline, Embase and The Cochrane Library databases were systematically searched for articles published from January 1980 to December 2013. We computed the summary proportions for ovarian function preservation, ovarian cyst formation and metastatic ovarian disease following ovarian transposition by random effects meta-analysis with meta-regression to explore for heterogeneity by type of radiotherapy.ResultsTwenty four articles reporting on 892 women undergoing ovarian transposition were included. In the surgery alone group, the proportion of women with preserved ovarian function was 90% (95% CI 92–99), 87% (95% CI 79–97) of women did not develop ovarian cysts and 100% (95% CI 90–111) did not suffer metastases to the transposed ovaries. In the brachytherapy (BR) ± surgery group, the proportion of women with preserved ovarian function was 94% (95% CI 79–111), 84% (95% CI 70–101) of women did not develop ovarian cysts and 100% (95% CI 85–118) did not suffer metastases to the transposed ovaries. In the external beam radiotherapy (EBRT) + surgery ± BR group, the proportion of women with preserved ovarian function was 65% (95% CI 56–74), 95% (95% CI 85–106) of women did not develop ovarian cysts and 100% (95% CI 90–112) did not suffer metastases to the transposed ovaries. Subgroup meta-analysis revealed transposition to the subcutaneous tissue being associated with higher ovarian cyst formation rate compared to the “traditional” transposition.ConclusionOvarian transposition is associated with significant preservation of ovarian function and negligible risk for metastases to the transposed ovaries despite common incidence of ovarian cysts.