Transcription factor 3 controls cell proliferation and migration in glioblastoma multiforme cell lines

2016 ◽  
Vol 94 (3) ◽  
pp. 247-255 ◽  
Author(s):  
Ruiting Li ◽  
Yinghui Li ◽  
Xin Hu ◽  
Haiwei Lian ◽  
Lei Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glioblastoma Multiforme ◽  
Cell Lines ◽  
Normal Brain ◽  
Phosphatidylinositol 3 Kinase ◽  
T Cell Factor ◽  
And Migration ◽  
Induced Apoptosis ◽  
Proliferation And Migration ◽  
Transcription Factor 3

Transcription factor 3 (TCF3) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family. Recent studies have demonstrated its potential carcinogenic properties. Here we show that TCF3 was upregulated in glioma tissues compared with normal brain tissues. This upregulation of the TCF3 gene probably has functional significance in brain-tumor progression. Our studies on glioblastoma multiforme (GBM) cell lines show that knock-down of TCF3 induced apoptosis and inhibited cell migration. Further analysis revealed that down-regulation of TCF3 gene expression inhibits Akt and Erk1/2 activation, suggesting that the carcinogenic properties of TCF3 in GBM are partially mediated by the phosphatidylinositol 3-kinase–Akt and MAPK–Erk signaling pathways. Considered together, the results of this study demonstrate that high levels of TCF3 in gliomas potentially promote glioma development through the Akt and Erk pathways.

scholarly journals Progression and Differentiation of Alveolar Rhabdomyosarcoma Is Regulated by PAX7 Transcription Factor—Significance of Tumor Subclones

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1870
Author(s):  
Klaudia Skrzypek ◽  
Grażyna Adamek ◽  
Marta Kot ◽  
Bogna Badyra ◽  
Marcin Majka
Keyword(s):  
Transcription Factor ◽  
Cell Lines ◽  
Migration Activity ◽  
Id Proteins ◽  
Rh30 Cell ◽  
Str Profile ◽  
And Migration

Rhabdomyosarcoma (RMS), is the most frequent soft tissue tumor in children that originates from disturbances in differentiation process. Mechanisms leading to the development of RMS are still poorly understood. Therefore, by analysis of two RMS RH30 cell line subclones, one subclone PAX7 negative, while the second one PAX7 positive, and comparison with other RMS cell lines we aimed at identifying new mechanisms crucial for RMS progression. RH30 subclones were characterized by the same STR profile, but different morphology, rate of proliferation, migration activity and chemotactic abilities in vitro, as well as differences in tumor morphology and growth in vivo. Our analysis indicated a different level of expression of adhesion molecules (e.g., from VLA and ICAM families), myogenic microRNAs, such as miR-206 and transcription factors, such as MYOD, MYOG, SIX1, and ID. Silencing of PAX7 transcription factor with siRNA confirmed the crucial role of PAX7 transcription factor in proliferation, differentiation and migration of RMS cells. To conclude, our results suggest that tumor cell lines with the same STR profile can produce subclones that differ in many features and indicate crucial roles of PAX7 and ID proteins in the development of RMS.

scholarly journals Contribution of transcription factor EB to adipoRon-induced inhibition of arterial smooth muscle cell proliferation and migration

2019 ◽  
Vol 317 (5) ◽  
pp. C1034-C1047 ◽  
Author(s):  
Yun-Ting Wang ◽  
Jiajie Chen ◽  
Xiang Li ◽  
Michihisa Umetani ◽  
Yang Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Remodeling ◽  
Therapeutic Effects ◽  
Transcription Factor Eb ◽  
And Migration ◽  
Proliferation And Migration

Abnormal vascular smooth muscle cell (SMC) dedifferentiation with increased proliferation and migration during pathological vascular remodeling is associated with vascular disorders, such as atherosclerosis and in-stent restenosis. AdipoRon, a selective agonist of adiponectin receptor, has been shown to protect against vascular remodeling by preventing SMC dedifferentiation. However, the molecular mechanisms that mediate adipoRon-induced SMC differentiation are not well understood. The present study aimed to elucidate the role of transcription factor EB (TFEB), a master regulator of autophagy, in mediating adipoRon’s effect on SMCs. In cultured arterial SMCs, adipoRon dose-dependently increased TFEB activation, which is accompanied by upregulated transcription of genes involved in autophagy pathway and enhanced autophagic flux. In parallel, adipoRon suppressed serum-induced cell proliferation and caused cell cycle arrest. Moreover, adipoRon inhibited SMC migration as characterized by wound-healing retardation, F-actin reorganization, and matrix metalloproteinase-9 downregulation. These inhibitory effects of adipoRon on proliferation and migration were attenuated by TFEB gene silencing. Mechanistically, activation of TFEB by adipoRon is dependent on intracellular calcium, but it is not associated with changes in AMPK, ERK1/2, Akt, or molecular target of rapamycin complex 1 activation. Using ex vivo aortic explants, we demonstrated that adipoRon inhibited sprouts that had outgrown from aortic rings, whereas lentiviral TFEB shRNA transduction significantly reversed this effect of adipoRon on aortic rings. Taken together, our results indicate that adipoRon activates TFEB signaling that helps maintain the quiescent and differentiated status of arterial SMCs, preventing abnormal SMC dedifferentiation. This study provides novel mechanistic insights into understanding the therapeutic effects of adipoRon on TFEB signaling and pathological vascular remodeling.

scholarly journals EXTH-64. SMALL GTPASES IN MENINGIOMAS: PROLIFERATION, MIGRATION, SURVIVAL, POTENTIAL TREATMENT AND INTERACTIONS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii101-ii101
Author(s):  
Christoph Kesseler ◽  
Julian Kahr ◽  
Natalie Waldt ◽  
Nele Stroscher ◽  
Josephine Liebig ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Lines ◽  
Small Gtpases ◽  
Potential Treatment ◽  
Rock Inhibitor ◽  
Meningioma Cell ◽  
And Migration ◽  
Proliferation And Migration

Abstract PURPOSE To evaluate the role of the small GTPases RhoA, Rac1 and Cdc42 in meningiomas as therapeutic targets and their interactions in meningiomas. EXPERIMENTAL DESIGN We analyzed expression of GTPases in human meningioma samples and meningioma cell lines of various WHO grades. Malignant IOMM-Lee meningioma cells were used to generate shRNA mediated knockdowns of GTPases RhoA, Rac1 or Cdc42 and to study knockdown effects on proliferation and migration, as well as analysis of cell morphology by confocal microscopy. The same tests were used to investigate effects of the two inhibitors Fasudil and EHT-1864 of malignant IOMM-Lee, KT21 and benign Ben-Men cells and the effects of these drugs on IOMM-Lee knockdown cells. The effects of GTPase knockdowns and Fasudil treatment were studied in terms of overall survival by intracranial xenografts of mice. Potential interactions of GTPases regarding NF2, mTOR and FAK-Paxillin were examined. RESULTS Small GTPases were upregulated in meningiomas of higher tumor grades. Reduced proliferation and migration could be achieved by GTPase knockdown in IOMM-Lee cells. Additionally, the ROCK-inhibitor Fasudil and Rac1-inhibitor EHT-1864 reduced proliferation in different meningioma cell lines and reduced proliferation and migration independent of GTPase knockdowns/status. Moreover, overall survival in vivo could also be increased by knockdowns of RhoA and Rac1 as well as Fasudil treatment. GTPase expression was affected dependent on the NF2 status but effects were not very distinct, indicating that NF2 is not strongly involved in GTPase regulation in meningiomas. In terms of mTOR and FAK-Paxillin signaling, each GTPase changes those pathways in a different manner. CONCLUSION Small GTPases are important effectors in meningioma proliferation and migration in vitro as well as survival in vivo and their inhibition should be considered as potential treatment option.

MYRF haploinsufficiency causes 46,XY and 46,XX disorders of sex development: bioinformatics consideration

2019 ◽  
Vol 28 (14) ◽  
pp. 2319-2329 ◽  
Author(s):  
Kohei Hamanaka ◽  
Atsushi Takata ◽  
Yuri Uchiyama ◽  
Satoko Miyatake ◽  
Noriko Miyake ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
De Novo ◽  
Clinical Symptoms ◽  
Disorders Of Sex Development ◽  
Sequencing Data ◽  
Causative Gene ◽  
Sex Development ◽  
And Migration ◽  
Proliferation And Migration

AbstractDisorders of sex development (DSDs) are defined as congenital conditions in which chromosomal, gonadal or anatomical sex is atypical. In many DSD cases, genetic causes remain to be elucidated. Here, we performed a case–control exome sequencing study comparing gene-based burdens of rare damaging variants between 26 DSD cases and 2625 controls. We found exome-wide significant enrichment of rare heterozygous truncating variants in the MYRF gene encoding myelin regulatory factor, a transcription factor essential for oligodendrocyte development. All three variants occurred de novo. We identified an additional 46,XY DSD case of a de novo damaging missense variant in an independent cohort. The clinical symptoms included hypoplasia of Müllerian derivatives and ovaries in 46,XX DSD patients, defective development of Sertoli and Leydig cells in 46,XY DSD patients and congenital diaphragmatic hernia in one 46,XY DSD patient. As all of these cells and tissues are or partly consist of coelomic epithelium (CE)-derived cells (CEDC) and CEDC developed from CE via proliferaiton and migration, MYRF might be related to these processes. Consistent with this hypothesis, single-cell RNA sequencing of foetal gonads revealed high expression of MYRF in CE and CEDC. Reanalysis of public chromatin immunoprecipitation sequencing data for rat Myrf showed that genes regulating proliferation and migration were enriched among putative target genes of Myrf. These results suggested that MYRF is a novel causative gene of 46,XY and 46,XX DSD and MYRF is a transcription factor regulating CD and/or CEDC proliferation and migration, which is essential for development of multiple organs.

scholarly journals USP13 Regulates the Breast Tumor Proliferation and Migration through the Stabilization of PDCD4 Protein

2021 ◽  
Author(s):  
Jun Tian ◽  
Bei Li ◽  
Jing Qiao ◽  
Xinfeng Pang ◽  
Xiaojing Yue
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Breast Tumor ◽  
Soft Agar ◽  
Tumor Proliferation ◽  
Soft Agar Assay ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract Background: Programmed cell death protein 4 (PDCD4), which serves as a tumor suppressor protein, plays a important role in cell proliferation,apoptosis, cell migration and DNA-damage response.However, the exact mechanism for the deubiquitination of PDCD4 remain unclear.Methods: Western blotting was used to detect the expression of PDCD4 in the breast cancer tissues and BC cell lines. We identified the potential PDCD4 associated deubiquitinase by RNAi screening. GST-Pull down and domain-mapping analysis were used to reveal that USP13 and PDCD4 directly interact with each other.Flow cytometry was used to detect the changes of G1 to S phase. Soft agar assay was used to measure the changes of the cell proliferation efficiency.Results: The expression of PDCD4 was decreased in the breast cancer tissues and BC cell lines. USP13 as a potential PDCD4 associated deubiquitinase. USP13 physically interacted with PDCD4 and greatly increased the steady state of PDCD4 through the ubiquitin-proteasome pathway.Importantly, silencing of the USP13 facilitated cell cycle from G1 to Sphase, promoted breast tumor cells proliferation and migration through downregulation of PDCD4. Conclusions: Together, these results suggest that USP13 plays an important role in the breast tumor proliferation and migration through modulating PDCD4 stability.

scholarly journals MiR-486-5p Suppresses Proliferation and Migration of Hepatocellular Carcinoma Cells through Downregulation of the E3 Ubiquitin Ligase CBL

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Jia He ◽  
Bin Xiao ◽  
Xiaoyan Li ◽  
Yongyin He ◽  
Linhai Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Ubiquitin Ligase ◽  
Target Genes ◽  
E3 Ubiquitin Ligase ◽  
Tumor Stage ◽  
Suppressor Gene ◽  
Cell Counting ◽  
And Migration ◽  
Proliferation And Migration

MicroRNAs have been broadly implicated in cancer, but precise functions and mechanisms in carcinogenesis vary among cancer types and in many cases remain poorly understood. Hepatocellular carcinoma (HCC) is among the most frequent and lethal cancers. The aim of the present study was to investigate the role of miR-486-5p in HCC and identify its specific target. MiR-486-5p was significantly downregulated in HCC tissues and cell lines compared with noncancerous tissues and, respectively, although expression level was not correlated with the degree of infiltration or tumor stage. However, miR-486-5p overexpression in HCC cells inhibited proliferation and migration as evidenced by CCK-8 cell counting, wound healing, and transwell assays, indicating that miR-486-5p is an HCC suppressor. We employed four miRNA databases to predict the target genes of miR-486-5p and verified retrieved genes using qPCR and western blotting. The E3 ubiquitin ligase CBL was significantly downregulated by miR-486-5p overexpression in HCC cell lines at both mRNA and protein level, and overexpression of CBL counteracted the inhibitory effects of miR-486-5p on HCC cell proliferation and migration. Moreover, CBL expression was negatively correlated with miR-486-5p expression in HCC tissues. Collectively, our results suggest that miR-486-5p may act as a tumor suppressor gene in HCC by downregulating CBL expression.

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