Clinically Relevant microRNAs in Ovarian Cancer

Zhang, Shu; Lü, Zhen; Unruh, Anna K.; Ivan, Cristina; Baggerly, Keith A.; Calin, George A.; Li, Zongfang; Bast, Robert C.; Le, Xiao Feng

doi:10.1158/1541-7786.mcr-14-0424

Cited by 90 publications

(79 citation statements)

References 74 publications

(113 reference statements)

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“…Correlations of genes previously identified to be associated with ovarian disease [34–41] (Supplemental Table S13) with the transgenerational granulosa cell genes of this study identified a number of genes associated with ovarian disease, Figure 11 and Supplemental Table S14. A gene that was present in the DDT and vinclozolin DMR associated genes and ovarian disease associated genes was Pkp4, plakophilins 4 [34,55].…”

Section: Discussionmentioning

confidence: 79%

“…Extensive reviews previously published have summarized the genes that have been associated with ovarian disease [34–41]. These published ovarian disease-associated genes were compiled into a list of 416 genes that are listed in Supplemental Table S13.…”

Section: Resultsmentioning

confidence: 99%

“…The specific overlapped genes are presented in Figure 11(C) and Table S14. Therefore, a number of ovarian disease-associated genes previously identified [34–41] were in common with the transgenerational granulosa cell DMRs and mRNA identified.

10.1080/15592294.2018.1521223-F0011Figure 11.Ovarian disease gene associations. (a) DMR associated gene overlap with published ovarian disease genes.…”

Section: Resultsmentioning

confidence: 99%

“…The Egr1 is associated with granulosa cell apoptosis during atresia through the NF-KB pathway [57]. The majority of transgenerational granulosa cell DMR associated genes and differentially expressed mRNA were not in common with these previously identified ovarian disease associated genes [34–41]. A more complete list of ovarian disease genes would likely have greater overlap.…”

Section: Discussionmentioning

confidence: 99%

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Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufficiency

et al. 2018

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Two of the most prevalent ovarian diseases affecting women’s fertility and health are Primary Ovarian Insufficiency (POI) and Polycystic Ovarian Syndrome (PCOS). Previous studies have shown that exposure to a number of environmental toxicants can promote the epigenetic transgenerational inheritance of ovarian disease. In the current study, transgenerational changes to the transcriptome and epigenome of ovarian granulosa cells are characterized in F3 generation rats after ancestral vinclozolin or DDT exposures. In purified granulosa cells from 20-day-old F3 generation females, 164 differentially methylated regions (DMRs) (P < 1 x 10−6) were found in the F3 generation vinclozolin lineage and 293 DMRs (P < 1 x 10−6) in the DDT lineage, compared to controls. Long noncoding RNAs (lncRNAs) and small noncoding RNAs (sncRNAs) were found to be differentially expressed in both the vinclozolin and DDT lineage granulosa cells. There were 492 sncRNAs (P < 1 x 10−4) in the vinclozolin lineage and 1,085 sncRNAs (P < 1 x 10−4) in the DDT lineage. There were 123 lncRNAs and 51 lncRNAs in the vinclozolin and DDT lineages, respectively (P < 1 x 10−4). Differentially expressed mRNAs were also found in the vinclozolin lineage (174 mRNAs at P < 1 x 10−4) and the DDT lineage (212 mRNAs at P < 1 x 10−4) granulosa cells. Comparisons with known ovarian disease associated genes were made. These transgenerational epigenetic changes appear to contribute to the dysregulation of the ovary and disease susceptibility that can occur in later life. Observations suggest that ancestral exposure to toxicants is a risk factor that must be considered in the molecular etiology of ovarian disease.

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Section: Discussionmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

10.1080/15592294.2018.1521223-F0011Figure 11.Ovarian disease gene associations. (a) DMR associated gene overlap with published ovarian disease genes.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufficiency

et al. 2018

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“…Zhang et al (16) reported that miRNA was involved in the occurrence and development of ovarian cancer drug resistance by studying a stem cell-like epithelial ovarian cancer line. Li et al (17) demonstrated that miRNA-27a was associated with ovarian cancer drug resistance, and the mechanism was that MDR1/P-GP gene regulated the HIPK2 gene.…”

Section: Discussionmentioning

confidence: 99%

Expression of microRNA-30a-5p in drug-resistant and drug-sensitive ovarian cancer cell lines

Liu

et al. 2016

Oncology Letters

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Abstract. The present study aimed to explore the expression of microRNA (miRNA or miR) in drug-resistant and drug-sensitive ovarian cancer cell lines, and to seek the potential therapeutic target of ovarian cancer drug-resistant mechanism in order to improve drug resistance by altering miRNA levels. The drug-resistant characteristics of SKOV3/DDP, SKOV3, COC1/DDP and COC1 cell lines were studied. The miRNAs that were differentially expressed between cisplatin-resistant cells and its parental cells in ovarian cancer were screened with a miRNA chip. The effect of miRNAs was detected, and their drug-resistant mechanism was investigated by transfection and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods. Among the expression screening of miRNAs, 41 mRNAs, including Homo sapiens (hsa)-miR-30a-5p and hsa-miR-34c-5p, were highly expressed in the drug-resistant cells, whereas 44 miRNAs, including hsa-miR-96-5p and hsa-miR-200c-3p, were lowly expressed. The expression levels of hsa-miR-30a-5p in two types of ovarian cancer chemotherapy-resistant cell lines were significantly higher than those in chemotherapy-sensitive cell lines, which was associated with ovarian cancer chemotherapy resistance. In conclusion, high expression of miRNA-30a-5p was able to promote cell growth and colony forming ability, and enhance cell migration and invasion. Thus, miRNA-30a-5p is expected to become a meaningful novel target for ovarian cancer resistant treatment.

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miRNAs and ovarian cancer: An overview

Deb

Uddin²,

Chakraborty

2017

Journal Cellular Physiology

168

121

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Ovarian cancer (OC) is the sixth most common cancer in women globally. However, even with the advances in detection and therapeutics it still represents the most dangerous gynecologic malignancy in women of the industrialized countries. The discovery of micro-RNAs (miRNA), a small noncoding RNA molecule targeting multiple mRNAs and regulation of gene expression by triggering translation repression and/or RNA degradation, has revealed the existence of a new array for regulation of genes involved in cancer. This review summarizes the current knowledge regarding the role of miRNAs expression in OC. It also provides information about potential clinical relevance of circulating miRNAs for OC diagnosis, prognosis, and therapeutics. The identification of functional targets for miRNAs represents a major obstacle in our understanding of microRNA function in OC, but significant progress is being made. The better understanding of the role of microRNA expression in ovarian cancer may provide new array for the detection, diagnosis, and therapy of the OC.

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Clinically Relevant microRNAs in Ovarian Cancer

Cited by 90 publications

References 74 publications

Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufficiency

Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufficiency

Expression of microRNA-30a-5p in drug-resistant and drug-sensitive ovarian cancer cell lines

miRNAs and ovarian cancer: An overview

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