scholarly journals LncRNA SRA mediates cell migration, invasion, and progression of ovarian cancer via NOTCH signaling and epithelial-mesenchymal transition

2021 ◽  
Author(s):  
Lee Kyung Kim ◽  
Sun-Ae Park ◽  
Yoolhee Yang ◽  
Young Tae Kim ◽  
Tae-Hwe Heo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Cancer Patients ◽  
Epithelial Mesenchymal Transition ◽  
Gynecological Cancer ◽  
Notch Pathway ◽  
Tumor Formation ◽  
High Expression ◽  
Free Survival ◽  
Mesenchymal Transition

Long non-coding RNA (lncRNA) is a newly identified regulator of tumor formation and tumor progression. The function and expression of lncRNAs remain to be fully elucidated, but recent studies have begun to address their importance in human health and disease. The lncRNA, SRA, known as Steroid receptor activator, acts as an important modulator of gynecological cancer, and its expression may affect biological functions including proliferation, apoptosis, steroid formation and muscle developments. However, it is still not well known whether SRA is involved in the regulation of ovarian cancer. This study investigated the molecular function and association between SRA expression and clinicopathological factors. In ovarian cancer cell lines, SRA knockdown and overexpression regulated cell migration, proliferation, and invasion. Both in vivo and in vitro experiments using knockdown and overexpression showed that SRA potently regulated epithelial-mesenchymal transition and NOTCH pathway components. Further, clinical data confirmed that SRA was a significant predictor of overall survival and progression-free survival and patients with ovarian cancer exhibiting high expression of SRA exhibited higher recurrence rates than patients with low SRA expression. In conclusion, this study indicates that SRA has clinical significance as its expression can predict the prognosis of ovarian cancer patients. High expression of the lncRNA SRA is strongly correlated with recurrence-free survival of ovarian cancer patients.

scholarly journals MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jin Wang ◽  
Lingxia Liu
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Gynecological Cancer ◽  
Gene Expression Omnibus ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract Background Ovarian cancer (OC), a kind of gynecological cancer, is characterized by high mortality rate, with microRNAs (miRNAs) playing essential roles in it. However, the clinical significance of miRNAs and their molecular mechanisms in OC are mostly unknown. Methods miR-149-3p expression was predicted through Gene Expression Omnibus (GEO) data in OC and confirmed by q-PCR in various OC cells and tissues from patients with different clinical characteristics. Moreover, its roles in terms of proliferation, migration and invasion were measured by CCK-8, colony formation, wound healing and transwell assays in OC cells including cisplatin-resistant and cisplatin-sensitive cells. And its effect on epithelial-mesenchymal transition was also assessed through detecting related protein expression. Additionally, its potential targets were verified by dual luciferase assay and Ago-RIP assay. Finally, its oncogenic functions were explored in vivo. Results In data from GSE79943, GSE131790, and TCGA, miR-149-3p was found to be highly expressed in OC tissues and associated with poor survival. In metastasis and chemoresistant tissues and cisplatin-resistant OC cells, its high expression was confirmed. In terms of tumorigenic effects, miR-149-3p knockdown in cisplatin-resistant OC cells inhibited its cisplatin resistance and other malignant phenotypes, while miR-149-3p overexpression in cisplatin-resistant OC cells led to contrary results. Mechanistically, miR-149-3p targeted 3’UTR of CDKN1A and TIMP2 to function as an oncogenic miRNA. Conclusion In brief, miR-149-3p promoted cisplatin resistance and EMT in OC by downregulating CDKN1A and TIMP2, which might provide a potential therapeutic target for OC treatment.

scholarly journals lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1

2018 ◽  
Vol 48 (5) ◽  
pp. 1928-1941 ◽  
Author(s):  
Chuan He ◽  
Zhigang Liu ◽  
Li Jin ◽  
Fang Zhang ◽  
Xinhao Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: MicroRNA-142-3p (miR-142-3p) is dysregulated in many malignancies and may function as a tumor suppressor or oncogene in tumorigenesis and tumor development. However, few studies have investigated the clinical significance and biological function of miR-142-3p in hepatocellular carcinoma (HCC). Methods: The expression levels of taurine upregulated gene 1 (TUG1), miR-142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC tissues and cell lines by quantitative real-time PCR. MTT and colony formation assays were used to detect cell proliferation ability, transwell assays were used to assess cell migration and invasion, and luciferase reporter assays were used to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p. Tumor formation was evaluated through in vivo experiments. Results: miR-142-3p was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell proliferation, cell migration, cell invasion, and the epithelial-mesenchymal transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT in nude mice. Conclusion: The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.

Differential Expression Pattern of Epithelial Mesenchymal Transition Gens; AXL, GAS6, Claudin-1, and Cofilin-1, in Different Stages of Epithelial Ovarian Cancer

2020 ◽  
Author(s):  
Elham HASSANI ◽  
Mahmood SHEKARI KHANIANI ◽  
Mojtaba SAFFARI ◽  
Amirnader EMAMI RAZAVI ◽  
Reza SHIRKOOHI ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Expression Pattern ◽  
Epithelial Mesenchymal Transition ◽  
Tnm Staging ◽  
Expression Level ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Differential Expression Pattern

Background: Epithelial ovarian cancer (EOC), is the fatal form of gynecological cancer. Almost 70% of ovarian cancer patients are detected at an advanced stage (III-IV) with metastases. Epithelial‑mesenchymal transition (EMT) is a critical process associated with metastasis. This study investigated the expression levels of AXL, GAS6, Claudin-1, and Cofilin-1, as genes involved in EMT in relation to clinicopathologic features in ovarian cancer patients. Methods: In this descriptive study, 78 ovarian epithelial cancer patients were enrolled. Samples were provided by the Iran National Tumor Bank, founded by the Cancer Institute of Tehran University of Medical Sciences in 2017. The expression levels of AXL, GAS6, Claudin-1, and Cofilin-1 genes were investigated in a fresh, frozen tumor sample and normal adjacent tissue by real-time PCR (RT-PCR). Results: Findings showed a significant relationship between the overexpression of AXL and TNM staging (P=0.03). The expression level of GAS6 decreased in more advanced stages (P=0.01). There is a negative relationship between Cofilin-1 expression level and TNM staging (P=0.002). Claudin-1 expression level was higher in low stages compared with that in high stages (P=0.01). There was no relationship between gene expression levels of target genes with size and grade of the tumor. Conclusion: Given the importance of these genes in EMT, alteration in their expression pattern can contribute to the progression of the disease and distant metastasis of cancer cells. Additionally, knowing the alteration pattern of these genes expression can help to better understanding and prediction of the prognosis of EOC.

Expression Profiles of Genes Involved in Poor Prognosis of Epithelial Ovarian Carcinoma: A Review

2009 ◽  
Vol 19 (6) ◽  
pp. 992-997 ◽  
Author(s):  
Shozo Yoshida ◽  
Naoto Furukawa ◽  
Shoji Haruta ◽  
Yasuhito Tanase ◽  
Seiji Kanayama ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Gynecological Cancer ◽  
Cancer Prognosis ◽  
Specific Expression ◽  
Mesenchymal Transition ◽  
Wide Range

Background:Epithelial ovarian cancer (EOC) is the commonest cause of gynecological cancer-related mortality. Although the prognosis for patients with advanced cancer is poor, there is a wide range of outcomes for individual patients.Objective:The aim of this study was to review molecular factors predictive of poor prognosis of women with EOC by reviewing microarray research identifying gene expression profiles.Methods:A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2008, combining the keywords "genome-wide," "microarray," "epithelial ovarian cancer" "prognosis," and "epithelial-mesenchymal transition" with specific expression profiles of genes.Results:Many genes that participated in cell signaling, growth factors, transcription factors, proteinases, metabolism, cell adhesion, extracellular matrix component, cell proliferation, and anti-apoptosis were overexpressed in patients with poor prognosis. Several important prognosis-related genes overlap with those known to be regulated by epithelial-mesenchymal transition (EMT). This signaling pathway of EMT (E-cadherin, β-catenin, receptor tyrosine kinases, NF-κB, TGF-β, or Wnt signalings) will be discussed, as it provides new insights into a new treatment strategy.Conclusions:This review summarizes recent advances in prognosis-related molecular biology. Collectively, molecular changes possibly through EMT are considered to be a major contributor to the poor prognosis of EOC.

scholarly journals Arctigenin Inhibits Cholangiocarcinoma Progression by Regulating Cell Migration and Cell Viability via the N-cadherin and Apoptosis Pathway

2021 ◽  
Author(s):  
Sutthiwan Janthamala ◽  
Apinya Jusakul ◽  
Sarinya Kongpetch ◽  
Phongsaran Kimawaha ◽  
Poramate Klanrit ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Viability ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
High Expression ◽  
Immunocytochemical Staining ◽  
Survival Times ◽  
Apoptosis Pathway ◽  
Mesenchymal Transition ◽  
The Impact

Abstract Northeast Thailand has the highest incidence of cholangiocarcinoma (CCA) in the world. The lack of promising diagnostic markers and appropriate therapeutic drugs are the main problem for metastatic stage CCA patients who have a poor prognosis. N-cadherin, a cell adhesion molecule, is usually upregulated in cancers and has been proposed as an important mediator in epithelial-mesenchymal transition (EMT), one of the metastasis processes. Additionally, it has been shown that arctigenin, a seed extract from Arctium lappa, can inhibit cancer cell progression via suppression of N-cadherin pathway. In this study, we investigated the protein expression of N-cadherin and its correlation with clinicopathological data of CCA patients, as well as the impact of arctigenin on KKU-213A and KKU-100 CCA cell lines and its underlying mechanisms. Immunohistochemistry results demonstrated that high expression of N-cadherin was significantly associated with severe CCA stage (p=0.027), and shorter survival time (p=0.002) of CCA patients. The mean overall survival times between low and high expression of N-cadherin were 31.6 and 14.8 months, respectively. Wound healing assays showed that arctigenin significantly inhibited CCA cell migration by downregulating N-cadherin whereas upregulating E-cadherin expression. Immunocytochemical staining revealed that arctigenin suppressed the expression of N-cadherin in both CCA cell lines. Furthermore, flow cytometry and western blot analysis revealed that arctigenin significantly reduced CCA cell viability and induced apoptosis via the Bax/Bcl-2/Caspase-3 pathway. This research supports the use of N-cadherin as a prognostic marker for CCA and arctigenin as a potential alternative therapy for improving CCA treatment outcomes.

scholarly journals The Overexpression of Keratin 23 Promotes Migration of Ovarian Cancer via Epithelial-Mesenchymal Transition

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Meng Ren ◽  
Yan Gao ◽  
Qi Chen ◽  
Hongyu Zhao ◽  
Xiaoting Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Background. Keratin 23 (KRT23) is a new member of the KRT gene family and known to be involved in the development and migration of various types of tumors. However, the role of KRT23 in ovarian cancer (OC) remains unclear. This study is aimed at investigating the function of KRT23 in OC. Methods. The expression of KRT23 in normal ovarian and OC tissues was determined using the Oncomine database and immunohistochemical staining. Reverse transcription quantitative polymerase chain reaction assay was used to analyze the expression of KRT23 in normal ovarian epithelial cell lines and OC cell lines. Small interfering RNA (siRNA), wound healing assay, and transwell assay were conducted to detect the effects of KRT23 on OC cell migration and invasion. Further mechanistic studies were verified by the Gene Expression Profiling Interactive Analysis platform, Western blotting, and immunofluorescence staining. Results. KRT23 was highly expressed in OC tissues and cell lines. High KRT23 expression could regulate OC cell migration and invasion, and the reduction of KRT23 by siRNA inhibited the migration and invasion of OC cells in vitro. Furthermore, KRT23 mediated epithelial-mesenchymal transition (EMT) by regulating p-Smad2/3 levels in the TGF-β/Smad signaling pathway. Conclusions. These results demonstrate that KRT23 plays an important role in OC migration via EMT by regulating the TGF-β/Smad signaling pathway.

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