scholarly journals The Biological and Clinical Role of the Long Non-Coding RNA LOC642852 in Ovarian Carcinoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5237 ◽  
Author(s):  
Natalie Filippov-Levy ◽  
Reuven Reich ◽  
Ben Davidson
Keyword(s):  
Matrix Metalloproteinase ◽  
Cell Signaling ◽  
Ovarian Carcinoma ◽  
Serous Carcinoma ◽  
Spheroid Formation ◽  
Clinical Role ◽  
Cerna Network ◽  
Non Coding Rna ◽  
Long Non Coding Rna

The objective of the present study was to analyze the biological and clinical role of the long non-coding RNA LOC642852 in ovarian carcinoma (OC). LOC642852 expression was analyzed in seven OC cell lines (OVCAR-3, OVCAR-8, OVCA 433, OVCA 429, OC 238, DOV13, ES-2) and 139 high-grade serous carcinoma (HGSC) specimens (85 effusions, 54 surgical specimens). Following LOC642852 knockout (KO) using the CRISPR/Cas9 system, OVCAR-8 HGSC cells were analyzed for spheroid formation, migration, invasion, proliferation, matrix metalloproteinase (MMP) activity, and expression of cell signaling proteins. OVCAR-8 cells with LOC642852 KO were significantly less motile and less invasive compared to controls, with no differences in spheroid formation, proliferation, or matrix metalloproteinase (MMP) activity. Total Akt and Erk levels were comparable in controls and KO cells, but their phosphorylation was significantly increased in the latter. In clinical specimens, LOC642852 was overexpressed in ovarian tumors and omental/peritoneal metastases compared to effusion specimens (p = 0.013). A non-significant trend for shorter overall (p = 0.109) and progression-free (p = 0.056) survival was observed in patients with HGSC effusions with high LOC642852 levels. Bioinformatics analysis showed potential roles for LOC642852 as part of the TLE3/miR-221-3p ceRNA network and in relation to the FGFR3 protein. In conclusion, LOC642852 inactivation via CRISPR/Cas9 affects cell signaling, motility, and invasion in HGSC cells. LOC642852 is differentially expressed in HGSC cells at different anatomical sites. Its potential role in regulating the TLE3/miR-221-3p ceRNA network and FGFR3 merits further research.

Expression and clinical role of long non-coding RNA in high-grade serous carcinoma

2018 ◽  
Vol 148 (3) ◽  
pp. 559-566 ◽  
Author(s):  
Natalie Filippov-Levy ◽  
Hallel Cohen-Schussheim ◽  
Claes G. Tropé ◽  
Thea E. Hetland Falkenthal ◽  
Yoav Smith ◽  
...  
Keyword(s):  
Serous Carcinoma ◽  
High Grade ◽  
Clinical Role ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Identification of long non-coding RNA HERC2P2 as a tumor suppressor in glioma

2019 ◽  
Vol 40 (8) ◽  
pp. 956-964 ◽  
Author(s):  
Chao Yang ◽  
Lin Wang ◽  
Jia Sun ◽  
Jun-hu Zhou ◽  
Yan-li Tan ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Survival Rates ◽  
Hect Domain ◽  
Cerna Network ◽  
Non Coding Rna ◽  
Potential Biomarker ◽  
Scratch Tests ◽  
Long Non Coding Rna

Abstract Long non-coding RNAs (lncRNAs) have been reported to play important roles in glioma; however, most of them promote glioma progression. We constructed a competing endogenous (ceRNA) network based on the Chinese Glioma Genome Atlas dataset, and lncRNA hect domain and RLD 2 pseudogene 2 (HERC2P2) is the core of this network. Highly connected genes in the ceRNA network classified the glioma patients into three clusters with significantly different survival rates. The expression of HERC2P2 is positively correlated with survival and negatively correlated with clinical grade. Cell colony formation, Transwell and cell scratch tests were performed to evaluate the role of HERC2P2 in glioblastoma growth. Furthermore, we overexpressed HERC2P2 in U87 cells and established a mouse intracranial glioma model to examine the function of HERC2P2 in vivo. In conclusion, we identified a lncRNA with tumor suppressor functions in glioma that could be a potential biomarker for glioma patients.

The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway

2017 ◽  
Vol 57 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Shuo Chen ◽  
Li-li Wang ◽  
Kai-Xuan Sun ◽  
Yin-ling Xiu ◽  
Zhi-Hong Zong ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Epithelial Ovarian Carcinoma ◽  
Non Coding Rna ◽  
Tumorigenesis And Progression ◽  
Long Non Coding Rna

scholarly journals Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

2017 ◽  
Vol 45 (1) ◽  
pp. 131-147 ◽  
Author(s):  
Yana Gao ◽  
Hai Yu ◽  
Yunhui Liu ◽  
Xiaobai Liu ◽  
Jian Zheng ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cell Viability ◽  
Malignant Glioma ◽  
Cell Lines ◽  
Vasculogenic Mimicry ◽  
Tube Formation ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Expression And Activity

Background/Aims: Vasculogenic mimicry (VM) has been reported to be a novel glioma neovascularization process. Anti-VM therapy provides new insight into glioma clinical management. In this study, we revealed the role of the long non-coding RNA HOXA cluster antisense RNA 2 (HOXA-AS2) in malignant glioma behaviors and VM formation. Methods: Quantitative real-time PCR was performed to determine the expression levels of HOXA-AS2 in glioma samples and glioblastoma cell lines. CD34-periodic acid-Schiff dual-staining was performed to assess VM in glioma samples. CCK-8, transwell, and Matrigel tube formation assays were performed to measure the effects of HOXA-AS2 knockdown on cell viability, migration, invasion, and VM tube formation, respectively. RNA immunoprecipitation, dual-luciferase reporter and Western blot assays were performed to explore the molecular mechanisms underlying the functions of HOXS-AS2 in glioblastoma cells. A nude mouse xenograft model was used to investigate the role of HOXA-AS2 in xenograft glioma growth and VM density. Student’s t-tests, one-way ANOVAs followed by Bonferroni posthoc tests, and chi-square tests were used for the statistical analyses. Results: HOXA-AS2 was upregulated in glioma samples and cell lines and was positively correlated with VM. HOXA-AS2 knockdown attenuated cell viability, migration, invasion, and VM formation in glioma cells and inhibited the expression of vascular endothelial-cadherin (VE-cadherin), as well as the expression and activity of matrix metalloproteinase matrix metalloproteinase (MMP)-2 and MMP-9. miR-373 was downregulated in glioma samples and cell lines and suppressed malignancy in glioblastoma cells. HOXA-AS2 bound to miR-373 and negatively regulated its expression. Epidermal growth factor receptor (EGFR), a target of miR-373, increased the expression levels of VE-cadherin, as well as the expression and activity levels of MMP-2 and MMP-9, via activating phosphatidylinositol 3-kinase/serine/threonine kinase pathways. HOXA-AS2 knockdown combined with miR-373 overexpression yielded optimal tumor suppressive effects and the lowest VM density in vivo. Conclusion: HOXA-AS2 knockdown inhibited malignant glioma behaviors and VM formation via the miR-373/EGFR axis.

scholarly journals The Biological Role of the Long Non-coding RNA LINK-A in Ovarian Carcinoma

2020 ◽  
Vol 40 (12) ◽  
pp. 6677-6684
Author(s):  
NATALIE FILIPPOV-LEVY ◽  
BEN DAVIDSON ◽  
REUVEN REICH
Keyword(s):  
Ovarian Carcinoma ◽  
Biological Role ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Role of the Exosome Secretion Machinery in Ovarian Carcinoma: In Vitro and In Vivo Models

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Esther Channah Broner ◽  
Hadil Onallah ◽  
Tali Tavor Re’em ◽  
Ben Davidson ◽  
Reuven Reich
Keyword(s):  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Carcinoma Cells ◽  
Serous Carcinoma ◽  
Clinical Role ◽  
In Vivo Models ◽  
Ovarian Carcinoma Cells

Objective. We recently reported on the expression and clinical role of molecules that mediate exosome secretion in high-grade serous carcinoma. In the present study, the biological role of these molecules was analyzed. Methods. OVCAR8 and ES-2 ovarian carcinoma cells were studied using a combination of CRISPR/Cas9 technology and two 3D in vitro models—spheroids emulating effusions and alginate scaffolds representing solid lesions. Isolation of exosomes was validated by electron microscopy. TSAP6, NSMASE2, RAB27A, and RAB27B mRNA and protein levels were analyzed using qRT-PCR and Western blotting, respectively. Tumor aggressiveness was studied in vitro using scratch assay, invasion assay, and matrix metalloproteinase (MMP) activity assay and in vivo using a mouse model. Results. In OVCAR8 cells, mRNA expression of TSAP6 and RAB27A was significantly higher in spheroids compared to scaffolds, whereas the opposite was true for NSMASE2 mRNA. In ES-2 cells, TSAP6 and RAB27B mRNA expression was significantly higher in spheroids versus scaffolds. In addition, nSMase2 and TSAP6 protein expression was significantly higher in scaffolds compared to spheroids. CRISPR-edited cells with silencing of NSMASE2, TSAP6, and RAB27A/B had reduced migration, invasion, and MMP activity. Additionally, knockout (KO) of these molecules resulted in significantly diminished exosome secretion. In vivo assay showed that when injected to mice, OVCAR8 RAB27A/B KO cells, as opposed to control OVCAR8 cells, did not form ascites or visible tumor lesions and had reduced MMP expression. Conclusion. The present study provides evidence that different models for culturing ovarian carcinoma cells affect the expression of molecules mediating exosome secretion and that these molecules have a tumor-promoting role. Silencing these molecules may consequently have therapeutic relevance in this cancer.

scholarly journals Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0171661 ◽  
Author(s):  
Federica Conte ◽  
Giulia Fiscon ◽  
Matteo Chiara ◽  
Teresa Colombo ◽  
Lorenzo Farina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Cerna Network ◽  
Non Coding Rna ◽  
Long Non Coding Rna

The role of long non-coding RNA PCA3 in epithelial ovarian carcinoma tumorigenesis and progression

Gene ◽  
2017 ◽  
Vol 633 ◽  
pp. 42-47 ◽  
Author(s):  
Yao Liu ◽  
Zhi-Hong Zong ◽  
Xue Guan ◽  
Li-li Wang ◽  
Yang Zhao
Keyword(s):  
Ovarian Carcinoma ◽  
Epithelial Ovarian Carcinoma ◽  
Non Coding Rna ◽  
Tumorigenesis And Progression ◽  
Long Non Coding Rna

scholarly journals Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Chemotherapeutic Response ◽  
Non Coding Rna ◽  
Response To Chemotherapy ◽  
Personalized Oncology ◽  
Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

scholarly journals LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression

2021 ◽  
Vol 16 (1) ◽  
pp. 1-13
Author(s):  
Weiwei Liu ◽  
Dongmei Yao ◽  
Bo Huang
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Nude Mouse Model ◽  
Western Blot Assay ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 in vivo. PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth in vivo. PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.

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