miRNA‐301b‐3p accelerates migration and invasion of high‐grade ovarian serous tumor via targeting CPEB3/EGFR axis

2019 ◽  
Vol 120 (8) ◽  
pp. 12618-12627 ◽  
Author(s):  
Fengying Liu ◽  
Guilian Zhang ◽  
Shiming Lv ◽  
Xinmian Wen ◽  
Peishu Liu
Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 492 ◽  
Author(s):  
Weder Pereira de Menezes ◽  
Viviane Aline Oliveira Silva ◽  
Izabela Natália Faria Gomes ◽  
Marcela Nunes Rosa ◽  
Maria Luisa Corcoll Spina ◽  
...  

The 5’-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients’ clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients’ clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP’s role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.


2017 ◽  
Vol 70 ◽  
pp. 98-104 ◽  
Author(s):  
Florence A. Arts ◽  
Lisa Keogh ◽  
Paul Smyth ◽  
Sharon O'Toole ◽  
Robert Ta ◽  
...  

2018 ◽  
Vol 16 (8) ◽  
pp. 1226-1240 ◽  
Author(s):  
Jessica Tang ◽  
Nicholas Pulliam ◽  
Ali Özeş ◽  
Aaron Buechlein ◽  
Ning Ding ◽  
...  

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi249-vi250
Author(s):  
Thuvarahan Jegathees ◽  
Victoria Prior ◽  
Geraldine O’Neill

Abstract A major limitation in the treatment of High Grade Gliomas (HGG) is their highly disseminating nature. While it is increasingly appreciated that the mechanical properties of the extracellular matrix, (measured as tissue elasticity, Young’s modulus, E), can independently cue cancer cell migration and invasion, to date there has been little consideration of this mechanism in HGG invasion. This is particularly important given that the brain parenchyma is a mechanically soft tissue (E values varying between 1 - 10 kPa). By measuring single cell migration we have previously demonstrated that molecular subclasses of HGGs exhibit different rigidity-sensitive and -insensitive migration. Following these findings, the present project aimed to determine whether these mechanosensitive phenotypes are maintained in the dissemination of multicellular tumour spheroids (MCTSs) that represent in vivo organisation of the primary tumour bulk. Therefore MCTSs composed of primary patient-derived HGG cells with pre-established single cell mechanosensitive phenotypes were cultured on mechanically tuneable polyacrylamide hydrogels, mimicking the range of physiological tissue rigidities. Bright-field time-lapse images were then captured over a period of 48 hours, 6 images per hour. In order to quantitate the migratory behaviours, we adapted a previously published automated image analysis program to segment the MCTS images into proliferative and migratory regions. Our analysis suggests that the cellular mechano-phenotype is affected by contact with neighbouring cells, as the migratory response to tissue stiffness is quantitatively different in the MCTSs. Our results highlight different migratory behaviour between HGG cells within the primary tumour mass versus individual cells that escape. Our results reveal the complex migratory behaviour of HGG cells and suggests that successful anti-invasive therapies will need different strategies depending on tumour cell location.


2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Xiaomei Sun ◽  
Lingtong Hou ◽  
Chunping Qiu ◽  
Beihua Kong

Abstract Background Several studies have shown the crucial role of miR-501 in regulating cellular pathology in various cancers. However, the function and expression of miR-501 in endometrial cancer (EC) remain obscure. Methods The expression of miR-501 was determined using quantitative real-time PCR. MTT assay, colony formation assay and cell cycle analysis were used to evaluate the proliferation ability. Migration and invasion were assessed using transwell assay. Tumor formation in nude mice was used to observe the effects of miR-501 on cell proliferation and migration in vivo. Luciferase assay, quantitative real-time PCR and western blot were applied to determine that HOXD10 was the target gene of miR-501. Results In this study, we observed significantly up-regulated expression of miR-501 in endometrial cancer, which correlated with higher pelvic lymph node metastasis and shorter overall survival in high-grade endometrial cancer. High expression of miR-501 was also found in the copy-number-high group than other groups. Moreover, in vitro and in vivo assay showed that overexpression of miR-501 can promote proliferation and metastasis. Mechanistically, we found that miR-501 promotes tumor progression by directly targeting HOXD10. Further study also indicated that miR-501 overexpression can activate the AKT/mTOR pathway. Conclusions MiR-501, which functions as an oncomir in endometrial cancer, might be a potential therapeutic target in high grade endometrial cancer.


2016 ◽  
Vol 150 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Joeri Both ◽  
Thijs Wu ◽  
Anneloor L.M.A. ten Asbroek ◽  
Frank Baas ◽  
Theo J.M. Hulsebos

Osteosarcomas are primary tumors of bone that most often develop in adolescents. They are characterized by complex genomic changes including amplifications, deletions, and translocations. The chromosome region 17p11.2p12 is frequently amplified in human high grade osteosarcomas (25% of cases), suggesting the presence of one or more oncogenes. In previous studies, we identified 9 candidate oncogenes in this region (GID4, ARGHAP44, LRRC75A-AS1, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1). The aim of the present study was to determine their oncogenic properties. Therefore, we generated osteosarcoma cell lines overexpressing these genes, except for LRRC75A-AS1 and PRPSAP2, and subjected these to functional oncogenic assays. We found that TOP3A, SHMT1, and RASD1 overexpression provided increased proliferation and that ARGHAP44, COPS3, and PMP22 overexpression had a stimulatory effect on migration and invasion of the cells. COPS3 and PMP22 overexpression additionally improved the ability of the cells to form new colonies. No oncogenic effect could be demonstrated for GID4 overexpression. We conclude that the concerted amplification-mediated overexpression of these genes in 17p11.2p12 may contribute to the oncogenic process in malignant osteosarcoma.


PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0168418 ◽  
Author(s):  
Andrew S. Gilder ◽  
Lei Wang ◽  
Letizia Natali ◽  
Nicki Karimi-Mostowfi ◽  
Coralie Brifault ◽  
...  

2022 ◽  
Author(s):  
Zhiyuan Sun ◽  
Yufu Zhu ◽  
Xia Feng ◽  
Xiaoyun Liu ◽  
Kunlin Zhou ◽  
...  

Abstract H3.3K27M is a newly identified molecular pathology marker in glioma and is especially correlated with the malignancy of diffuse intrinsic pontine glioma (DIPG). In recent years, accumulating research has revealed that other types of glioma also contain the H3.3K27M mutation. However, the role of H3.3K27M in high-grade adult glioma, which is the most malignant glioma, has not been investigated. In this study, we focused on exploring the expression and function of H3.3K27M in high-grade adult glioma patients. We found that H3.3K27M is partly highly expressed in high-grade glioma tissues. Then, we introduced H3.3K27M into H3.3 wild-type glioma cells, U87 cells and LN229 cells. We found that H3.3K27M did not regulate the growth of glioma in vitro and in vivo; however, the survival of mice with transplanted tumors was significantly reduced. Further investigation revealed that H3.3K27M expression mainly promoted the migration and invasion of glioma cells. Moreover, we certified that H3.3K27M overexpression enhanced the protein levels of ꞵ-catenin and p-ꞵ-catenin, the protein and mRNA levels of ubiquitin-specific protease 1 (USP1), and the protein level of enhancer of zeste homolog 2 (EZH2). Importantly, the ꞵ-catenin inhibitor XAV-939 significantly attenuated the upregulation of the aforementioned proteins. Overall, the H3.3K27M mutation is present in a certain proportion of high-grade glioma patients and facilitates a poor prognosis by promoting the metastasis of glioma by regulating the ꞵ-catenin/USP1/EZH2 pathway.


2019 ◽  
Vol Volume 12 ◽  
pp. 6371-6383 ◽  
Author(s):  
Minmin Zhang ◽  
Feifei Li ◽  
Jing Wang ◽  
Wenzhu He ◽  
Yun Li ◽  
...  

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