scholarly journals Differential Expression Profiles and Function Prediction of Transfer RNA-Derived Fragments in High-Grade Serous Ovarian Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Buze Chen ◽  
Sicong Liu ◽  
Haihong Wang ◽  
Guilin Li ◽  
Xiaoyuan Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Target Genes ◽  
Unsaturated Fatty Acids ◽  
Expression Profiles ◽  
Transfer Rna ◽  
Differentially Expressed ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Glycosphingolipid Biosynthesis

Background. The present study is aimed at providing systematic insight into the composition and expression of transfer RNA (tRNA) derivative transcription in high-grade serous ovarian cancer (HGSOC). Methods. tRNA derivative expression profiles in three pairs of HGSOC and adjacent normal ovarian tissues were conducted by tRNA-derived small RNA fragment (tRF) and tRNA half (tiRNA) sequencing. The differentially expressed tRFs and tiRNAs between HGSOC and paired adjacent normal samples were screened. The targeted genes of differentially expressed tRFs and tiRNAs were screened. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) of target genes of tRFs and tiRNAs were analyzed. Results. There are a total of 20 significantly upregulated and 15 significantly downregulated tRFs and tiRNAs between the cancer group and the paracarcinoma group. The upregulated tRFs and tiRNAs are mucin-type O-glycan biosynthesis, glycosphingolipid biosynthesis, the glucagon signaling pathway, the AMPK signaling pathway, maturity-onset diabetes of the young, glycosphingolipid biosynthesis, the insulin signaling pathway, insulin resistance, leukocyte transendothelial migration, starch, and sucrose metabolism. The downregulated tRFs and tiRNAs are other glycan degradation, vitamin digestion and absorption, fatty acid elongation, and biosynthesis of unsaturated fatty acids. Conclusions. There are significantly expressed tRFs and tiRNAs in HGSOC tissues, and these may provide potential diagnostic biomarkers and therapeutic targets for HGSOC.

scholarly journals Odd-skipped related 2 (OSR2) is differentially expressed in high-grade serous ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Cell Fate ◽  
Microarray Data ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Differentially Expressed ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Primary Tumors ◽  
Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2,3). We previously identified forkhead box L2 (4), (FOXL2) as among the genes whose expression was most different in HGSC ovarian tumors when compared to the ovary. Here, we find that potential FOXL2 transcriptional target (5,6) odd-skipped related gene OSR2 (7) is differentially expressed in high-grade serous ovarian cancer, and could be observed in independent tumor microarray data (2,3). These data reveal perturbed expression of a target gene of a key transcription factor and specifier of ovarian cell fate in high-grade serous ovarian cancers.

scholarly journals Frizzled class 7 receptor is differentially expressed in high-grade serous ovarian cancer and based on patient survival.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Progression Free Survival ◽  
Global Gene Expression ◽  
Differentially Expressed ◽  
Published Data ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Free Survival

High-grade serous ovarian cancer (HGSC) is the most common type of the most lethal gynecologic malignancy (1). To identify genes whose expression was associated with survival outcomes in HGSC, we used published data from patients enrolled in the ICON7 trial to compare the global gene expression profiles of primary HGSC tumors from women with the best and worst progression-free survival (PFS) (2). We found that the Frizzled class 7 (Fzd7) receptor was among the genes most differentially expressed in HGSC tumors when comparing tumor transcriptomes based on superior or inferior PFS. In two independent datasets, Fzd7 was among the genes most differentially expressed in HGSC tumors when comparing primary tumor to the normal ovary (3, 4). Wnt pathway signaling through Fzd7 may be relevant to the biology of high-grade serous ovarian cancers.

scholarly journals Traf5 is differentially expressed in high-grade serous ovarian cancer and based on patient survival.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Patient Survival ◽  
Expression Profiles ◽  
Ovarian Tissue ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Differentially Expressed ◽  
High Grade ◽  
Serous Ovarian Cancer

High-grade serous ovarian cancer (HGSC) is the most common type of the most lethal gynecologic malignancy (1). To identify genes whose expression was specifically perturbed in HGSC, we used published microarray data (2, 3) to compare the global gene expression profiles of primary HGSC tumors to normal ovarian tissue. We found that the TNF receptor associated factor 5 (TRAF5) (4, 5) was among the genes most differentially expressed in HGSC tumors relative to the normal ovary. In a separate dataset from patients enrolled in the ICON7 trial (6), the Traf5 gene was among those most differentially expressed when comparing HGSC tumor gene expression based on patient survival outcomes. Traf5 may be relevant to the biology of high-grade serous ovarian cancers.

scholarly journals A cell-of-origin epigenetic tracer reveals clinically distinct subtypes of high-grade serous ovarian cancer

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Pietro Lo Riso ◽  
Carlo Emanuele Villa ◽  
Gilles Gasparoni ◽  
Andrea Vingiani ◽  
Raffaele Luongo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Differentially Expressed ◽  
Prognostic Impact ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Tumor Subtypes ◽  
Transcriptional Alterations ◽  
Bona Fide ◽  
Tissue Of Origin

Abstract Background High-grade serous ovarian cancer (HGSOC) is a major unmet need in oncology. The remaining uncertainty on its originating tissue has hampered the discovery of molecular oncogenic pathways and the development of effective therapies. Methods We used an approach based on the retention in tumors of a DNA methylation trace (OriPrint) that distinguishes the two putative tissues of origin of HGSOC, the fimbrial (FI) and ovarian surface epithelia (OSE), to stratify HGSOC by several clustering methods, both linear and non-linear. The identified tumor subtypes (FI-like and OSE-like HGSOC) were investigated at the RNAseq level to stratify an in-house cohort of macrodissected HGSOC FFPE samples to derive overall and disease-free survival and identify specific transcriptional alterations of the two tumor subtypes, both by classical differential expression and weighted correlation network analysis. We translated our strategy to published datasets and verified the co-occurrence of previously described molecular classification of HGSOC. We performed cytokine analysis coupled to immune phenotyping to verify alterations in the immune compartment associated with HGSOC. We identified genes that are both differentially expressed and methylated in the two tumor subtypes, concentrating on PAX8 as a bona fide marker of FI-like HGSOC. Results We show that: - OriPrint is a robust DNA methylation tracer that exposes the tissue of origin of HGSOC. - The tissue of origin of HGSOC is the main determinant of DNA methylation variance in HGSOC. - The tissue of origin is a prognostic factor for HGSOC patients. - FI-like and OSE-like HGSOC are endowed with specific transcriptional alterations that impact patients’ prognosis. - OSE-like tumors present a more invasive and immunomodulatory phenotype, compatible with its worse prognostic impact. - Among genes that are differentially expressed and regulated in FI-like and OSE-like HGSOC, PAX8 is a bona fide marker of FI-like tumors. Conclusions Through an integrated approach, our work demonstrates that both FI and OSE are possible origins for human HGSOC, whose derived subtypes are both molecularly and clinically distinct. These results will help define a new roadmap towards rational, subtype-specific therapeutic inroads and improved patients’ care.

scholarly journals RNA-Seq Reveals the Expression Profiles of Long Non-Coding RNAs in Lactating Mammary Gland from Two Sheep Breeds with Divergent Milk Phenotype

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1565
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jiang Hu ◽  
Xiu Liu ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Signaling Pathway ◽  
Target Genes ◽  
Mammary Epithelial Cells ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Mammary Epithelial ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are a kind of non-coding RNA with >200 nucleotides in length. Some lncRNAs have been proven to have clear regulatory functions in many biological processes of mammals. However, there have been no reports on the roles of lncRNAs in ovine mammary gland tissues. In the study, the expression profiles of lncRNAs were studied using RNA-Seq in mammary gland tissues from lactating Small-Tailed Han (STH) ewes and Gansu Alpine Merino (GAM) ewes with different milk yield and ingredients. A total of 1894 lncRNAs were found to be expressed. Compared with the GAM ewes, the expression levels of 31 lncRNAs were significantly up-regulated in the mammary gland tissues of STH ewes, while 37 lncRNAs were remarkably down-regulated. Gene Ontogeny (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the target genes of differentially expressed lncRNAs were enriched in the development and proliferation of mammary epithelial cells, morphogenesis of mammary gland, ErbB signaling pathway, and Wnt signaling pathway. Some miRNA sponges of differentially expressed lncRNAs, reported to be associated with lactation and mammary gland morphogenesis, were found in a lncRNA-miRNA network. This study reveals comprehensive lncRNAs expression profiles in ovine mammary gland tissues, thereby providing a further understanding of the functions of lncRNAs in the lactation and mammary gland development of sheep.

scholarly journals Molecular Profiling and Clinical Outcome of High-Grade Serous Ovarian Cancer Presenting with Low- versus High-Volume Ascites

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Tomer Feigenberg ◽  
Blaise Clarke ◽  
Carl Virtanen ◽  
Anna Plotkin ◽  
Michelle Letarte ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Clinical Outcome ◽  
Expression Profiles ◽  
High Volume ◽  
High Grade ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Immune Response Genes ◽  
Low Volume

Epithelial ovarian cancer consists of multiple histotypes differing in etiology and clinical course. The most prevalent histotype is high-grade serous ovarian cancer (HGSOC), which often presents at an advanced stage frequently accompanied with high-volume ascites. While some studies suggest that ascites is associated with poor clinical outcome, most reports have not differentiated between histological subtypes or tumor grade. We compared genome-wide gene expression profiles from a discovery cohort of ten patients diagnosed with stages III-IV HGSOC with high-volume ascites and nine patients with low-volume ascites. An upregulation of immune response genes was detected in tumors from patients presenting with low-volume ascites relative to those with high-volume ascites. Immunohistochemical studies performed on tissue microarrays confirmed higher expression of proteins encoded by immune response genes and increased tumorinfiltrating cells in tumors associated with low-volume ascites. Comparison of 149 advanced-stage HGSOC cases with differential ascites volume at time of primary surgery indicated low-volume ascites correlated with better surgical outcome and longer overall survival. These findings suggest that advanced stage HGSOC presenting with low-volume ascites reflects a unique subgroup of HGSOC, which is associated with upregulation of immune related genes, more abundant tumor infiltrating cells and better clinical outcomes.

scholarly journals Identification of hydatidosis-related modules and key regulatory genes

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9280
Author(s):  
Jijun Song ◽  
Mingxin Song
Keyword(s):  
Transcription Factors ◽  
Signaling Pathway ◽  
Target Genes ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Bmp Signaling ◽  
Differentially Expressed ◽  
Regulatory Effects

Background Echinococcosis caused by larval of Echinococcus is prevalent all over the world. Although clinical experience showed that the presence of tapeworms could not be found in liver lesions, the repeated infection and aggravation of lesions still occur in the host. Here, this study constructed a multifactor-driven disease-related dysfunction network to explore the potential molecular pathogenesis mechanism in different hosts after E.multilocularis infection. Method First, iTRAQ sequencing was performed on human liver infected with E.multilocularis. Second, obtained microRNAs(miRNAs) expression profiles of humans and canine infected with Echinococcus from the GEO database. In addition, we also performed differential expression analysis, protein interaction network analysis, enrichment analysis, and crosstalk analysis to obtain genes and modules related to E.multilocularis infection. Pivot analysis is used to calculate the potential regulatory effects of multiple factors on the module and identify related non-coding RNAs(ncRNAs) and transcription factors(TFs). Finally, we screened the target genes of miRNAs of Echinococcus to further explore its infection mechanism. Results A total of 267 differentially expressed proteins from humans and 3,635 differentially expressed genes from canine were obtained. They participated in 16 human-related dysfunction modules and five canine-related dysfunction modules, respectively. Both human and canine dysfunction modules are significantly involved in BMP signaling pathway and TGF-beta signaling pathway. In addition, pivot analysis found that 1,129 ncRNAs and 110 TFs significantly regulated human dysfunction modules, 158 ncRNAs and nine TFs significantly regulated canine dysfunction modules. Surprisingly, the Echinococcus miR-184 plays a role in the pathogenicity regulation by targeting nine TFs and one ncRNA in humans. Similarly, miR-184 can also cause physiological dysfunction by regulating two transcription factors in canine. Conclusion The results show that the miRNA-184 of Echinococcus can regulate the pathogenic process through various biological functions and pathways. The results laid a solid theoretical foundation for biologists to further explore the pathogenic mechanism of Echinococcosis.

scholarly journals PEG3 is differentially expressed in high-grade serous ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Gene Expression Profiles ◽  
Ovarian Tumors ◽  
Differentially Expressed ◽  
High Grade ◽  
Normal Ovary ◽  
Primary Tumors ◽  
Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1-3). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (4, 5). We identified paternally expressed gene 3 (PEG3) (6) as among the genes whose expression was most different in HGSC ovarian tumors. PEG3 expression was significantly lower in ovarian tumors relative to normal ovary. In one dataset, an anti-sense transcript produced at the PEG3 locus was among those most differentially expressed between HGSC tumors and benign ovarial tissue. These data indicate that significant changes in expression at the PEG3 imprinted locus could be a feature of high-grade serous ovarian cancers.

scholarly journals MiR-585-3p suppresses tumor proliferation and migration by directly targeting CAPN9 in high grade serous ovarian cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoyuan Lu ◽  
Guilin Li ◽  
Sicong Liu ◽  
Haihong Wang ◽  
Buze Chen
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Target Genes ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Aberrant Expression ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Aberrant expression of microRNAs (miRNAs) contributes to the development of high grade serous ovarian cancer (HGSOC). However, the molecular mechanism by which miRNA-585-3p mediates high-grade serous ovarian carcinogenesis is unclear. This study aims to investigate the specific mechanism of action of miR-585-3p in HGSOC. Methods Expression of miR-585-3p in HGSOC tissues and cell lines was detected by qRT-PCR. Cell viability and migration were detected using MTT and transwell system. The expression of target genes and target proteins of miR-585-3p was detected by dual luciferase reporter assay and western blot. Results The expression of miR-585-3p was significantly lower in HGSOC tissues and cells than in normal ovarian tissues and cell lines. In HGSOC tissues, CAPN9 expression was inversely correlated with miR-585-3p expression. MiR-585-3p inhibited the proliferation and migration of HGSOC cells. MiR-585-3p bound to the 3'-untranslated region (UTR) of CAPN9 and inhibits CAPN9 expression. Overexpression of CAPN9 reduced the inhibitory effect of miR-585-3p in HGSOC cells. Conclusions miR-585-3p is significantly down-regulated in HGSOC tissues and cell lines. MiR-585-3p inhibits the proliferation and migration of HGSOC cells by targeting CAPN9.

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