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.

scholarly journals Circ_0000020 elevates the expression of PIK3CA and facilitates the malignant phenotypes of glioma cells via targeting miR-142-5p

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xu Wang ◽  
Yaozu Zhu
Keyword(s):  
Glioma Cell ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Brain ◽  
Loss Of Function ◽  
Qrt Pcr ◽  
Glioma Progression

Abstract Background Multiple circular RNAs (circRNAs) have been recently described as crucial oncogenic factors or tumor suppressors. This study aimed to investigate the role of circ_0000020 in glioma progression. Methods Circ_0000020 and miR-142-5p expressions in glioma samples were assessed through qRT-PCR, and then the association between pathological indexes and circ_0000020 expressions was analyzed. Functional experiment was performed with human glioma cell lines U251 and U87. Gain-of-function and loss-of-function models were established. CCK-8 assay was used to detect glioma cell proliferation. Transwell assay was used to examine glioma cell migration and invasion. The regulatory relationships among circ_0000020, miR-142-5p and phosphatidylinositol 3-kinase C (PIK3CA) were investigated by bioinformatics analysis, luciferase reporter assay, qRT-PCR and Western blot. In vivo tumorigenesis assay was performed with nude mice to further validate the demonstrations of in vitro experiments. Results Circ_0000020 expression in glioma samples was remarkably increased compared with that in normal brain tissues and its high expression was associated with unfavorable pathological indexes. Circ_0000020 overexpression remarkably accelerated proliferation, migration and invasion of glioma cells. Accordingly, circ_0000020 knockdown suppressed the malignant phenotypes of glioma cells. Circ_0000020 overexpression significantly reduced miR-142-5p expression by sponging it, and circ_0000020 could enhance the expression of PIK3CA, which was a target gene of miR-142-5p. Conclusions Circ_0000020 promotes glioma progression via miR-142-5p/PIK3CA axis.

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 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 lncRNA LINC00355 Acts as a Novel Biomarker and Promotes Glioma Biological Activities via the Regulation of miR-1225/FNDC3B

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Zhen-yong Qi ◽  
Li-li Wang ◽  
Xu-liang Qu
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Biological Activities ◽  
Glioma Cells ◽  
Disease Free Survival ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Glioma Cell Lines

Background. Accumulating evidence has implicated long noncoding RNAs (lncRNAs) in glioma progression. Here, we aimed to explore the potential roles of a novel lncRNA, LINC00355, in glioma and to clarify the underlying mechanisms. Methods. RT-PCR was used to examine the relative expressions of LINC00355 in glioma cell lines and specimen samples. The clinicopathological and prognostic significances of LINC00355 in glioma patients were statistically analyzed. To determine cell activities, CCK-8, clonogenic assays, flow cytometry, migration, and invasion assays were performed. Moreover, the potential mechanisms of LINC00355 were investigated by bioinformatics assays and luciferase reporter assays. Results. LINC00355 expression was increased in glioma cell lines and specimens, and higher LINC00355 expression predicted advanced clinical progress and reduced overall survival and disease-free survival in glioma patients. Functionally, LINC00355 depletion promoted cell proliferation, invasion, and migration in glioma cells and induced apoptosis of glioma cells, whereas LINC00355 upregulation resulted in the opposite effects in vitro. Mechanistic assays revealed that LINC00355 as a sponge for miR-1225 repressed fibronectin type III domain-containing 3B (FNDC3B) expressions. Conclusion. Our findings revealed the tumor-promotive roles of LINC00355 in the progression of glioma, indicating that LINC00355 exhibited ceRNA functions via modulating miR-1225/FNDC3B axis.

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.

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 EXTH-03. HUMAN GLIOMA CELL MIGRATION AND INVASION PROPERTIES ARE INHIBITED BY EXPOSURE TO TUMOR TREATING FIELDS (TTFIELDS) IN VITRO

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi60-vi60
Author(s):  
Rosa Schneiderman ◽  
Anna Shteingauz ◽  
Moshe Giladi ◽  
Tali Voloshin ◽  
Yaara Porat ◽  
...  
Keyword(s):  
Cell Migration ◽  
Glioma Cell ◽  
Migration And Invasion ◽  
Human Glioma ◽  
Cell Migration And Invasion ◽  
Human Glioma Cell ◽  
Tumor Treating Fields ◽  
Glioma Cell Migration

scholarly journals The Long Intergenic Noncoding RNA 00707 Sponges MicroRNA-613 (miR-613) to Promote Proliferation and Invasion of Gliomas

2020 ◽  
Vol 19 ◽  
pp. 153303382096209
Author(s):  
Handong Liu ◽  
Keqi Hu
Keyword(s):  
Glioma Cell ◽  
Glioma Cells ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Clinicopathological Parameters ◽  
Migration And Invasion ◽  
Qrt Pcr ◽  
Non Coding Rna ◽  
Gene Assay ◽  
Proliferation And Invasion

Background: Glioma is one of the most deadly malignant tumors in humans. Long non-coding RNA (lncRNA) plays a key role in the occurrence, development and invasion of tumors by regulating oncogenic and tumor suppressor pathways. However, the role and action mechanism of long intergenic non-coding RNA 00707 (LINC00707) in gliomas have not been elucidated. This study aimed to investigate the interaction between LINC00707 and miR-613 as well as its role in gliomas. Materials and Methods: The expression levels of LINC00707 and miR-613 were detected by qRT-PCR. The chi-square test was used to analyze the correlation between LINC00707 expression and clinicopathological parameters. CCK-8 and colony formation assays were used to detect glioma cell proliferation; and wound healing and transwell assays were used to detect glioma cell migration and invasion. The relationship between LINC00707 and miR-613 was predicted by Starbase, and verified by qRT-PCR and dual luciferase reporter gene assay. Results: LINC00707 was up-regulated in gliomas. Up-regulated LINC00707 increased the proliferation, migration and invasion of glioma cells, and silenced LINC00707 reduced these abilities. The increase of the expression level of LINC00707 down-regulated miR-613 in glioma cells, while the inhibition of the expression level of LINC00707 up-regulated miR-613 in glioma cells. The high expression of LINC00707 was related to the Karnofsky performance status (KPS) score and WHO staging. LINC00707 could offset the ability of miR-613 to inhibit glioma proliferation and invasion. Conclusion: LINC00707 promotes proliferation and invasion of glioma cells by sponging miR-613. The regulatory axis of LINC00707/miR-613 provides new insights into the mechanism and treatment of gliomas.

scholarly journals miR-29a sensitizes the response of glioma cells to temozolomide by modulating the P53/MDM2 feedback loop

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiudan Chen ◽  
Weifeng Wang ◽  
Shuying Chen ◽  
Xiaotong Chen ◽  
Yong Lin
Keyword(s):  
Molecular Mechanism ◽  
Feedback Loop ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Aberrant Expression ◽  
Altered Expression ◽  
P53 Signaling

AbstractRecently, pivotal functions of miRNAs in regulating common tumorigenic processes and manipulating signaling pathways in brain tumors have been recognized; notably, miR‐29a is closely associated with p53 signaling, contributing to the development of glioma. However, the molecular mechanism of the interaction between miR-29a and p53 signaling is still to be revealed. Herein, a total of 30 glioma tissues and 10 non-cancerous tissues were used to investigate the expression of miR‐29a. CCK-8 assay and Transwell assay were applied to identify the effects of miR-29a altered expression on the malignant biological behaviors of glioma cells in vitro, including proliferation, apoptosis, migration and invasion. A dual-luciferase reporter assay was used to further validate the regulatory effect of p53 or miR-29a on miR-29a or MDM2, respectively, at the transcriptional level. The results showed that miR-29a expression negatively correlated with tumor grade of human gliomas; at the same time it inhibited cell proliferation, migration, and invasion and promoted apoptosis of glioma cells in vitro. Mechanistically, miR-29a expression was induced by p53, leading to aberrant expression of MDM2 targeted by miR-29a, and finally imbalanced the activity of the p53-miR-29a-MDM2 feedback loop. Moreover, miR-29a regulating p53/MDM2 signaling sensitized the response of glioma cells to temozolomide treatment. Altogether, the study demonstrated a potential molecular mechanism in the tumorigenesis of glioma, while offering a possible target for treating human glioma in the future.

Sign in / Sign up

Export Citation Format

Share Document