scholarly journals Berberine Inhibits Glioma Cell Migration and Invasion by Suppressing TGF-β1/COL11A1 Pathway and Enhances Chemosensitivity

2021 ◽  
Author(s):  
Yuxue Sun ◽  
Haiyan Huang ◽  
Zhixin Zhan ◽  
Haijun Gao ◽  
Chaochao Zhang ◽  
...  
Keyword(s):  
Nude Mice ◽  
Glioma Cell ◽  
High Throughput Sequencing ◽  
Glioma Cells ◽  
Isoquinoline Alkaloid ◽  
Migration And Invasion ◽  
Collagen Accumulation ◽  
Glioma Cell Migration ◽  
Tgf Β1

Abstract Background: The expression of collagen type XI alpha 1 chain (COL11A1) is up-regulated in many cancers, affecting the risk of metastasis, drug resistance, and poor prognosis. Berberine is an isoquinoline alkaloid present in many traditional Chinese medicines and it has been shown to reduce collagen accumulation in pulmonary fibrosis, diabetic nephropathy and arthritis. However, its effect on COL11A1 in glioma needs to be further elucidated.Methods: Western blot was performed to detect the expression level of COL11A1 in several glioma cells, and siCOL11A1 was performed to investigate the effect of COL11A1 on the migration and invasion ability of glioma cells. CCK-8, wound healing experiment and transwell experiment were performed to detect the effect of berberine on the proliferation, migration and invasion of glioma cells. The xenografts experiment in nude mice was performed to test the effect of berberine on inhibiting glioma in vivo.Results: Our results showed that COL11A1 is highly expressed in glioma cell lines and associated with migration, invasion, and chemoresistance of glioma cells. Knocking down COL11A1 caused decreased expression of MMPs, Snail, and MGMT. Berberine could inhibit the migration and invasion of glioma cells by suppressing the TGF-β1/COL11A1 pathway and changes actin cytoskeleton arrangement. In addition, berberine increased the chemosensitivity of glioma cells to temozolomide, which may be related to the down-regulation of Snail and MGMT proteins caused by berberine. High-throughput sequencing of xenografts in nude mice also showed that berberine inhibited the expression of COL11A1 in vivo.Conclusions: Our results suggest that berberine that targets COL11A1 to inhibit glioma migration, invasion and chemoresistance, may serve as a promising candidate for the development of anti-glioma drugs in the future.

scholarly journals Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

2021 ◽  
Author(s):  
Xuyang Lv ◽  
Jiangchuan Sun ◽  
Linfeng Hu ◽  
Ying Qian ◽  
Chunlei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Self Renewal

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

scholarly journals Long non-coding RNA linc00645 promotes TGF-β-induced epithelial–mesenchymal transition by regulating miR-205-3p-ZEB1 axis in glioma

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Chenlong Li ◽  
Hongshan Zheng ◽  
Weiliang Hou ◽  
Hongbo Bao ◽  
Jinsheng Xiong ◽  
...  
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Vital Role ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition

Abstract Accumulating evidence indicates long noncoding RNAs (lncRNA) play a vital role in tumor progression. However, the role of linc00645-induced accelerated malignant behavior in glioblastoma (GBM) remains unknown. In the present study, linc00645 expression was significantly upregulated in GBM tissues and cell lines. High level of linc00645 was associated with poor overall survival in GBM patients. Knockdown of linc00645 suppressed the proliferation, stemness, migration, invasion, and reversed transforming growth factor (TGF)-β-induced motility of glioma cell lines. Furthermore, linc00645 directly interacted with miR-205-3p and upregulated of miR-205-3p impeded efficiently the increase of ZEB1 induced by linc00645 overexpression. Moreover, knockdown of linc00645 significantly suppressed the progression of glioma cells in vivo. miR-205-3p was a target of linc00645 and linc00645 modulates TGF-β-induced glioma cell migration and invasion via miR-205-3p. Taken together, our findings identified the linc00645/miR-205-3p/ZEB1 signaling axis as a key player in EMT of glioma cells triggered by TGF-β. These data elucidated that linc00645 plays an oncogenic role in glioma and it may serve as a prognostic biomarker and a potential therapeutic target for the treatment of glioma in humans.

scholarly journals Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

2021 ◽  
Author(s):  
Xuyang Lv ◽  
Jiangchuan Sun ◽  
Linfeng Hu ◽  
Ying Qian ◽  
Chunlei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Self Renewal

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

miR-56a Mediates the Wnt/β-Catenin Pathway to Promote the Efficacy of Radiation on Glioma

2021 ◽  
Vol 11 (10) ◽  
pp. 1955-1960
Author(s):  
Min Chen ◽  
Heping Zhou ◽  
Jun Mao ◽  
Zhihong Li ◽  
Zhengjiang Zha
Keyword(s):  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Biological Processes ◽  
Array Analysis ◽  
Mirna Array ◽  
Qrt Pcr ◽  
The Impact ◽  
Glioma Cell Migration

Clarification of the miR-56a-mediated effect of Wnt/β-catenin pathway in glioma cells on radiosensitization. miRNA arrays were used to analyze the differential expression of miRNAs in biopsies from glioma patients. qRT-PCR to detect the levels of miR-56a and Wnt/β-catenin expressed in glioma cells and tissues. Evaluation of the impact of miR-56a on cell growth, invasion, and migrationforming ability by MTT assay and colony formation experiments. To analyze the involvement of miR-56a-mediated Wnt/β-catenin pathway in glioma biological processes and to examine the impact of miR-56a in glioma cell radiosensitivity. After miRNA array analysis, we found that miR-56a expression was significantly increased, and further studies showed that ectopic miR-56a expression in glial cells was sensitive to radiotherapy. miR-56a induction of Wnt/β-catenin promotes the upregulation of Parp in glioma cells. miR-56a can promote glioma cell migration and invasion in vitro as an important potential target for glioma disease.

Glioma cell migration and invasion as potential target for novel treatment strategies

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Ulrike Naumann ◽  
Patrick Harter ◽  
Jennifer Rubel ◽  
Elena Ilina ◽  
Anna-Eva Blank ◽  
...  
Keyword(s):  
Cell Migration ◽  
Glioma Cell ◽  
Treatment Strategies ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Perivascular Spaces ◽  
Existing Structures ◽  
Preclinical Treatment ◽  
The Brain ◽  
Glioma Cell Migration

AbstractDiffuse human gliomas constitute a group of most treatment-refractory tumors even if maximum treatment strategies including neurosurgical resection followed by combined radio-/chemotherapy are applied. In contrast to most other neoplasms, diffusely infiltrating gliomas invade the brain along pre-existing structures such as axonal tracts and perivascular spaces. Even in cases of early diagnosis single or small clusters of glioma cells are already encountered far away from the main tumor bulk. Complex interactions between glioma cells and the surrounding extracellular matrix and considerable changes in the cytoskeletal apparatus are prerequisites for the cellular movement of glioma cells through the brain thereby escaping from most current treatments. This review provides an overview about classical and current concepts of glioma cell migration/invasion and promising preclinical treatment approaches.

scholarly journals Downregulation of TET1 Promotes Glioma Cell Proliferation and Invasion by Targeting Wnt/β-Catenin Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jianwen Ji ◽  
Qiuxiang You ◽  
Jidong Zhang ◽  
Yutao Wang ◽  
Jing Cheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Adult Brain ◽  
Migration And Invasion ◽  
Downstream Targets ◽  
Glioma Cell Proliferation

Glioma is the most common malignant tumor in adult brain characteristic with poor prognosis and low survival rate. Despite the application of advanced surgery, chemotherapy, and radiotherapy, the patients with glioma suffer poor treatment effects due to the complex molecular mechanisms of pathological process. In this paper, we conducted the experiments to prove the critical roles TET1 played in glioma and explored the downstream targets of TET1 in order to provide a novel theoretical basis for clinical glioma therapy. RT-qPCR was adopted to detect the RNA level of TET1 and β-catenin; Western blot was taken to determine the expression of proteins. CCK8 assay was used to detect the proliferation of glioma cells. Flow cytometry was used to test cell apoptosis and distribution of cell cycle. To detect the migration and invasion of glioma cells, wound healing assay and Transwell were performed. It was found that downregulation of TET1 could promote the proliferation migration and invasion of glioma cells and the concomitant upregulation of β-catenin, and its downstream targets like cyclinD1 and c-myc were observed. The further rescue experiments were performed, wherein downregulation of β-catenin markedly decreases glioma cell proliferation in vitro and in vivo. This study confirmed the tumor suppressive function of TET1 and illustrated the underlying molecular mechanisms regulated by TET1 in glioma.

scholarly journals ELF1 upregulates MEIS1 to accelerate proliferation, migration and invasion of glioma cells through the GFI1/FBW7 axis

2020 ◽  
Author(s):  
Meixiong Cheng ◽  
Yi Zeng ◽  
Tian Zhang ◽  
Min Xu ◽  
Yaqiu Wu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Nude Mice ◽  
Cell Apoptosis ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Differential Analysis ◽  
Regulatory Pathways ◽  
In Vivo Experiments

Abstract Background: To explore whether the transcription factor ELF1 affects the GFI1-FBW7 through MEIS1, thus participating in the occurrence and development of glioma. In this study, key transcription factors were identified by differential analysis of GEO database, and downstream regulatory pathways were predicted by available literature.Methods and results: Based on bioinformatics analysis and existing studies, we speculate that the transcription factor ELF1 may regulate FBW7 through MEIS1-mediated GFI1 and thus affect the occurrence of glioma. The expressions of transcription factors ELF1, MEIS1 and GFI1 were up-regulated in glioma tissues, and the prognosis of glioma patients with high expression of ELF1 was worse.We found that interfering with ELF1 expression in glioma cells can reduce the proliferation, migration and invasion of tumor cells and induce cell apoptosis. The results of Western-blot showed that the expressions of PCNA and MMP9 were decreased, while the expression of cleaved caspase-3 was up-regulated. ChIP experiments showed that ELF1 binds to the MEIS1 promoter region, and MEIS1 can activate the enhancer of GFI1. In vivo experiments were carried out in nude mice, the results showed that interfering ELF1 could inhibit tumor growth in nude mice through the MEIS1-GFI1/FBW7.Conclusion: Therefore, interference of ELF1 in glioma can reduce its ability to recruit the transcription factor MEIS1, and further impair the activation ability of MEIS1 to GFI1 enhancer, which resulting in suppression of proliferation, migration and invasion and induction of cell apoptosis in glioma cells.

scholarly journals Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jia-Huang Liu ◽  
Qi-Fei Wu ◽  
Jun-Ke Fu ◽  
Xiang-Ming Che ◽  
Hai-Jun Li
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Nude Mice ◽  
Serum Glucose ◽  
Migration And Invasion ◽  
Endocrine Effect

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly ( P < 0.05 ); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly ( P < 0.05 ) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly ( P < 0.05 ); YAP and MMP9 mRNA expression increased significantly ( P < 0.05 ) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.

scholarly journals An E3 Ubiquitin Ligase RNF139 Serves as a Tumor-Suppressor in Glioma

2021 ◽  
Author(s):  
Xiaofeng Chen ◽  
Weiping Kuang ◽  
Yong Zhu ◽  
Bin Zhou ◽  
Xiaosong Li ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Ubiquitin Ligase ◽  
Glioma Cell ◽  
Protein Modification ◽  
E3 Ubiquitin Ligase ◽  
Ring Finger ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Tissue Samples

AbstractGlioma is highly lethal because of its high malignancy. Ubiquitination, a type of ubiquitin-dependent protein modification, has been reported to play an oncogenic or tumor-suppressive role in glioma development, depending on the targets. Ring finger protein 139 (RNF139) is a membrane-bound E3 ubiquitin ligase serving as a tumor suppressor by ubiquitylation-dependently suppressing cell growth. Herein, we firstly confirmed the abnormal downregulation of RNF139 in glioma tissues and cell lines. In glioma cells, ectopic RNF139 overexpression could inhibit, whereas RNF139 knockdown could aggravate the aggressive behaviors of glioma cells, including hyperproliferation, migration, and invasion. Moreover, in two glioma cell lines, RNF139 overexpression inhibited, whereas RNF139 knockdown enhanced the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and AKT serine/threonine kinase 1 (AKT). In a word, we demonstrate the aberration in RNF139 expression in glioma tissue samples and cell lines. RNF139 serves as a tumor-suppressor in glioma by inhibiting glioma cell proliferation, migration, and invasion and promoting glioma cell apoptosis through regulating PI3K/AKT signaling.

scholarly journals Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2204
Author(s):  
Meng-Die Yang ◽  
Yang Sun ◽  
Wen-Jun Zhou ◽  
Xiao-Zheng Xie ◽  
Qian-Mei Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cell Viability ◽  
Synergistic Effects ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

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