scholarly journals Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1

2021 ◽  
Vol 18 (11) ◽  
pp. 5741
Author(s):  
Sheril June Ankasha ◽  
Mohamad Nasir Shafiee ◽  
Norhazlina Abdul Wahab ◽  
Raja Affendi Raja Ali ◽  
Norfilza Mohd Mokhtar
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Untranslated Region ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Binding Motif ◽  
Skov3 Cell ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Dlc1 Expression

High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer with highly metastatic properties. A small non-coding RNA, microRNA (miRNA) was discovered to be a major regulator in many types of cancers through binding at the 3′-untranslated region (3′UTR), leading to degradation of the mRNA. In this study, we sought to investigate the underlying mechanisms involved in the dysregulation of miR-200c-3p in HGSC progression and metastasis. We identified the upregulation of miR-200c-3p expression in different stages of HGSC clinical samples and the downregulation of the tumor suppressor gene, Deleted in Liver Cancer 1 (DLC1), expression. Over expression of miR-200c-3p in HGSC cell lines downregulated DLC1 but upregulated the epithelial marker, E-cadherin (CDH1). Based on in silico analysis, two putative binding sites were found within the 3′UTR of DLC1, and we confirmed the direct binding of miR-200c-3p to the target binding motif at position 1488–1495 bp of 3′UTR of DLC1 by luciferase reporter assay in a SKOV3 cell line co-transfected with vectors and miR-200c-3p mimic. These data showed that miR-200c-3p regulated the progression of HGSC by regulating DLC1 expression post-transcription and can be considered as a promising target for therapeutic purposes.

scholarly journals Orthogonal proteomic platforms and their implications for the stable classification of high-grade serous ovarian cancer subtypes

2019 ◽  
Author(s):  
Stefani N. Thomas ◽  
Betty Friedrich ◽  
Michael Schnaubelt ◽  
Daniel W. Chan ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Large Scale ◽  
Clinical Samples ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cancer Subtypes ◽  
Data Independent Acquisition ◽  
Proteomic Approach ◽  
Liquid Chromatography Tandem Mass ◽  
Isobaric Tagging

SummaryThe National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) has established a two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS) workflow using isobaric tagging to compare protein abundance across samples. The workflow has been used for large-scale clinical proteomic studies with deep proteomic coverage within and outside of CPTAC. SWATH-MS, an instance of data-independent acquisition (DIA) proteomic methods, was recently developed as an alternate proteomic approach. In this study, we analyzed remaining aliquots of peptides using SWATH-MS from the original retrospective TCGA samples generated for the CPTAC ovarian cancer proteogenomic study (Zhang et al., 2016). The SWATH-MS results indicated that both methods confidently identified differentially expressed proteins in enriched pathways associated with the robust Mesenchymal subtype of high-grade serous ovarian cancer (HGSOC) and the homologous recombination deficient tumors also present in the original study. The results demonstrated that SWATH/DIA-MS presents a promising complementary or orthogonal alternative to the CPTAC harmonized proteomic method, with the advantages of simpler, faster, and cheaper workflows, as well as lower sample consumption. However, the SWATH/DIA-MS workflow resulted in shallower proteome coverage. Overall, we concluded that both analytical methods are suitable to characterize clinical samples such as in the high-grade serous ovarian cancer study, providing proteomic workflow alternatives for cancer researchers depending on the specific goals and context of the studies.

scholarly journals Low expression of circular RNA hsa_circ_0078607 predicts poor prognosis in high-grade serous ovarian cancer

2020 ◽  
Author(s):  
Nan Zhang ◽  
Zhiyou Yang ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Jiani Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Prognostic Indicator ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Diagnosis And Prognosis ◽  
Low Expression

Abstract Background Ovarian cancer remains one of the most lethal malignancies in women which is typically diagnosed at a late stage and has no effective screening strategy. It is essential to explore novel biomarkers for the diagnosis and prognosis of ovarian cancer, as well as therapeutic targets. Recent studies have shown that circRNAs participate in ovarian cancer progression by regulating various processes and being able to act as potential biomarkers for ovarian cancer diagnosis and prognosis. In the present study we aimed to explore the prognostic role of circ_0078607 in high-grade serous ovarian cancer. Results The expression of circ_0078607 in 49 high-grade serous ovarian cancer and adjacent non-cancerous tissue samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). We noticed that circ_0078607 expression was significantly downregulated in ovarian cancer tissues compared with adjacent non-cancerous tissues. Besides, patients with low circ_0078607 expression exhibited parameters associated with poor prognosis, including advanced FIGO stage and higher serum CA125 level. Kaplan-Meier survival curve analysis showed that both progression-free survival and overall survival were significantly shortened in patients with low circ_0078607 expression. Cox regression model analysis showed that low expression of circ_0078607 was an adverse prognostic indicator for high-grade serous ovarian cancer patients. Conclusions Low expression of circ_0078607 might be an adverse prognostic indicator for high-grade serous ovarian cancer patients.

scholarly journals Targeting the Microenvironment in High Grade Serous Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 266 ◽  
Author(s):  
Nkechiyere Nwani ◽  
Livia Sima ◽  
Wilberto Nieves-Neira ◽  
Daniela Matei
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Malignant Ascites ◽  
Cancer Cell Proliferation ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Secreted Factors ◽  
Peritoneal Tumor ◽  
Tumor Dissemination ◽  
Cellular Components

Cancer–stroma interactions play a key role in cancer progression and response to standard chemotherapy. Here, we provide a summary of the mechanisms by which the major cellular components of the ovarian cancer (OC) tumor microenvironment (TME) including cancer-associated fibroblasts (CAFs), myeloid, immune, endothelial, and mesothelial cells potentiate cancer progression. High-grade serous ovarian cancer (HGSOC) is characterized by a pro-inflammatory and angiogenic signature. This profile is correlated with clinical outcomes and can be a target for therapy. Accumulation of malignant ascites in the peritoneal cavity allows for secreted factors to fuel paracrine and autocrine circuits that augment cancer cell proliferation and invasiveness. Adhesion of cancer cells to the mesothelial matrix promotes peritoneal tumor dissemination and represents another attractive target to prevent metastasis. The immunosuppressed tumor milieu of HGSOC is permissive for tumor growth and can be modulated therapeutically. Results of emerging preclinical and clinical trials testing TME-modulating therapeutics for the treatment of OC are highlighted.

scholarly journals UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 262 ◽  
Author(s):  
Laura Hardy ◽  
Amrita Salvi ◽  
Joanna Burdette
Keyword(s):  
Ovarian Cancer ◽  
Fallopian Tube ◽  
Cancer Progression ◽  
Drug Targets ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cell Of Origin ◽  
Pax8 Expression

High-grade serous ovarian cancer is a deadly disease that can originate from the fallopian tube or the ovarian surface epithelium. The PAX (paired box) genes PAX2 and PAX8 are lineage-specific transcription factors required during development of the fallopian tube but not in the development of the ovary. PAX2 expression is lost early in serous cancer progression, while PAX8 is expressed ubiquitously. These proteins are implicated in migration, invasion, proliferation, cell survival, stem cell maintenance, and tumor growth. Hence, targeting PAX2 and PAX8 represents a promising drug strategy that could inhibit these pro-tumorigenic effects. In this review, we examine the implications of PAX2 and PAX8 expression in the cell of origin of serous cancer and their potential efficacy as drug targets by summarizing their role in the molecular pathogenesis of ovarian cancer.

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.

scholarly journals Reduced Gonadotrophin Receptor Expression Is Associated with a More Aggressive Ovarian Cancer Phenotype

2020 ◽  
Vol 22 (1) ◽  
pp. 71
Author(s):  
Janelle Cheung ◽  
Noor A. Lokman ◽  
Riya D. Abraham ◽  
Anne M. Macpherson ◽  
Eunice Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Progression Free Survival ◽  
Receptor Expression ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cancer Phenotype

Follicle-stimulating hormone (FSH) and luteinising hormone (LH) play important roles in regulating cell growth and proliferation in the ovary. However, few studies have explored the expression of FSH and LH receptors (FSHR and LHCGR) in ovarian cancer, and their functional roles in cancer progression remain inconclusive. This study investigated the potential impact of both mRNA (FSHR, LHCGR) and protein (FSHR, LHCGR) expression on ovarian cancer progression using publicly available online databases, qRT-PCR (high grade serous ovarian cancers, HGSOC, n = 29 and benign ovarian tumors, n = 17) and immunohistochemistry (HGSOC, n = 144). In addition, we investigated the effect of FSHR and LHCGR siRNA knockdown on the pro-metastatic behavior of serous ovarian cancer cells in vitro. High FSHR or high LHCGR expression in patients with all subtypes of high-grade ovarian cancer was significantly associated with longer progression-free survival (PFS) and overall survival (OS). High FSHR protein expression was associated with increased PFS (p = 0.050) and OS (p = 0.025). HGSOC patients with both high FSHR and high LHCGR protein levels had the best survival outcome, whilst both low FSHR and low LHCGR expression was associated with poorest survival (p = 0.019). Knockdown of FSHR significantly increased the invasion of serous ovarian cancer cells (OVCAR3 and COV362) in vitro. LHCGR knockdown also promoted invasion of COV362 cells. This study highlights that lower FSHR and LHCGR expression is associated with a more aggressive epithelial ovarian cancer phenotype and promotes pro-metastatic behaviour.

scholarly journals Exosomal lncRNA SHNG7 Promotes High-Grade Serous Ovarian Cancer Progression and Function As ceRNA to Target Notch1 By Sponging miR-34a-5p

2021 ◽  
Author(s):  
Jing Cui ◽  
Xue Lu ◽  
Weiting Gu ◽  
Cunzhong Yuan ◽  
Hui Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Invasion And Migration ◽  
And Migration ◽  
Poor Outcomes ◽  
And Function ◽  
Cancer Tissues ◽  
Competitive Endogenous Rna

Abstract Serous ovarian cancer, especially high-grade serous ovarian cancer (HGSOC) has a high mortality rate, and its five-year survival rate is only 30%. The reason for the difficulty in diagnosis and treatment is that the origin and pathogenic mechanism of HGSOC are still poorly understood. In this study, we tried to explore the molecular mechanism of lncRNA SHNG7 in regulating proliferation, invasion and migration in HGSOC. The expression of lncRNA SHNG7 was upregulated in cancer tissues, and was closely correlated with poor outcomes. LncRNA SHNG7 promoted cell proliferation, invasion, migration and influenced the cell cycle of cancer cell lines. Furthermore, lncRNA SHNG7 could function as competitive endogenous RNA (ceRNA) via directly sponging of microRNA-34a-5p, which further regulating the expression of Notch 1. Moreover, lncRNA SHNG7 could be carried by exosomes and the exosomal lncRNA SHNG7 promoted angiopoiesis. Taken together, our results proved that lncRNA SHNG7 could function as ceRNA and contribute to HGSOC progression, which provided a novel prognostic and therapeutic marker for HGSOC.

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