Ovarian cancer is the most lethal malignancy in female patients, and chemoresistance is the major contribution to low over survival rate. We aim to investigate the correction between Sirt1 expression and chemoresistance in serous epithelial ovarian cancer (EOC) and prognosis significance of Sirt1. Immunochemistry was used to determine the location pattern and expression of Sirt1 in a total of 63 serous EOC patients (28 cases of chemoresistance patients and 35 chemosensitive).The relationship between Sirt1 expression and clinicopathological features of serous EOC was analyzed. Univariate analysis and multifactor logistic regression analysis were applied to investigate risk factor for chemoresistance. Cox proportional hazards regression model and Kaplan-Meier survival analysis were applied to determine the prognosis factor and survival time. Immunohistochemistry proved that over-expression of nuclear Sirt1 was related to chemoresistance (P = 0.039). Multivariate logistic regression analysis proved that the nuclear expression of Sirt1 (P = 0.018) and the lymph node metastasis (P = 0.037) was independent risk factors for chemoresistance in serous epithelial ovarian cancer. Multivariate Cox regression result indicated that expression of Sirt1 (P = 0.026, RR 2.434, 95 % CI 1.109-5.339) and stage (P = 0.005, RR 2.366, 95 % CI 1.288-4.345) was independent prognostic factors. Kaplan-Meier analysis showed that the survival rate is significantly decreased in the Sirt1 highly expressed group. Western blot result showed that the protein level of Sirt1 was significantly higher in chemoresistant group compared with in sensitive group. In conclusion, our results proved that over-expression of Sirt1 could play an important role in chemoresistance of serous EOC and could be a prognosis indicator for the patient's survival outcome.

BackgroundIncreasing evidence indicates that long noncoding RNAs (LncRNAs) play a key role in multiple pathological processes. It has been shown that LncRNA steroid receptor RNA activator (SRA) is elevated in peripheral blood of patients with polycystic ovary syndrome (PCOS). The aim of this study was to assess the effect of elevated LncRNA SRA on ovarian granular cells of mice in vitro.Material/MethodsWe firstly isolated granular cells from mouse ovaries and over-expressed the LncRNA SRA by means of lentiviral transfection in this cell line. Then, we assessed the effects of LncRNA SRA on granular cells through real-time PCR, CCK-8 assay, flow cytometry, Hoechst staining, and Western blot assay.ResultsWe demonstrated that elevated LncRNA SRA stimulated cell growth, changed distribution of cell cycle phases with increase of Cyclin B, Cyclin E, and Cyclin D1, and inhibited cell apoptosis with up-regulation of bcl2 and down-regulation of bax, cleaved-caspase 3, and cleaved-PARP. Moreover, the contents of estradiol (E2) and progesterone (PG) and expressions of their key enzymes (CYP19A1 and CYP11A1) were up-regulated following over-expression of LncRNA SRA.ConclusionsTaken together, our results indicate that abnormal LncRNA SRA may be a risk factor for evoking PCOS.

BackgroundWe aimed to examine the expression of miR-1307 in chemosensitive and chemoresistant epithelial ovarian cancer tissues and cell lines and to analyze the clinicopathological significance of miR-1307 in ovarian cancer.MethodsMicroRNA microarray was used to screen differentially expressed microRNAs between the chemosensitive and chemoresistant epithelial ovarian cancer tissues. RT-PCR was used to validate the candidate microRNA. The potential target genes and their enriched biological pathways of microRNA were also analyzed. Dual Luciferase Reporter Gene Assay was conducted to validate the regulation of miRNA-1307 on the 3’-UTR of DAPK3.ResultsmiRNA-1307 was up-regulated in the chemoresistant epithelial ovarian cancer tissues compared to the chemosensitive counterparts. The up-regulation of miRNA-1307 was not associated with menopause, tumor differentiation state, clinical stage, and lymph node metastasis of ovarian cancer. Gene ontology analysis of miR-1307 candidate target genes indicated that miR-1307 candidate target genes were enriched in the processes of cell proliferation and differentiation, nucleotide synthesis and metabolism, and lymphocytes activation.ConclusionOur results suggest that miRNA-1307 may play a role in the development of chemoresistance in ovarian cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-015-0143-5) contains supplementary material, which is available to authorized users.

a b s t r a c tMiR-134 has been reported to have a role in the development and progression of various cancers. In this study, we found that miR-134 expression was significantly decreased in chemo-resistant serous epithelial ovarian cancer (EOC) patients. Over-expression of miR-134 enhanced the sensitivity of SKOV3-TR30 cells to paclitaxel, and increased paclitaxel-induced apoptosis. Further, Pak2 was identified as a direct target of miR-134, and Pak2-specific siRNA increased cell inhibition rate and promoted paclitaxal-induced apoptosis. By regulating Pak2 expression, miR-134 could mediate Bad phosphorylation at Ser112 and Ser136, which affected cell survival and apoptosis. In conclusion, our findings indicate that repression of miR-134 and consequent up-regulation of Pak2 might contribute to paclitaxel resistance.

No abstract

The mechanism by which the transcription factors inhibit the miRNA expression in ovarian cancer chemoresistance is unclear. The present study investigated the mechanism underlying the transcriptional repression of miR-134 in chemoresistant serous epithelial ovarian cancer. The results demonstrate that NF-κB1, c-Rel, and ELK1 are involved as transcription factors in repressing miR-134 expression in paclitaxel-resistant ovarian cancer cells. Knockdown of these transcription factors led to increased miR-134 expression, resulting in increased apoptosis and inhibition of proliferation in SKOV3-TR30 cells. NF-κB1, c-Rel, and ELK1 mRNA expression was upregulated in chemoresistant specimens and negatively correlated with miR-134 expression. Kaplan–Meier analysis revealed that high nuclear expressions of NF-κB1, c-Rel, ELK1 were significantly associated with short survival in serous epithelial ovarian cancer patients. Finally, TAB1 was identified as a functional target of miR-134, and the expression of TAB1 was increased by the transcription factors of NF-κB1, c-Rel, and ELK1 via miR-134. Taken together, these results provide an insight into the mechanism of repressed miR-134 expression in chemoresistance of serous epithelial ovarian cancer.

No abstract

No abstract