scholarly journals TMEM158 promotes the proliferation and migration of glioma cells via STAT3 signaling in glioblastomas

2022 ◽  
Author(s):  
Jiabo Li ◽  
Xuya Wang ◽  
Lulu Chen ◽  
Jinhao Zhang ◽  
Yiming Zhang ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Human Glioma ◽  
Poor Overall Survival ◽  
Who Grade ◽  
Glioma Growth

AbstractGlioblastoma is the most common primary intracranial malignant tumor in adults and has high morbidity and high mortality. TMEM158 has been reported to promote the progression of solid tumors. However, its potential role in glioma is still unclear. Here, we found that TMEM158 expression in human glioma cells in the tumor core was significantly higher than that in noncancerous cells at the tumor edge using bioinformatics analysis. Cancer cells in patients with primary GBMs harbored significantly higher expression of TMEM158 than those in patients with WHO grade II or III gliomas. Interestingly, regardless of tumor grading, human glioma samples that were IDH1-wild-type (IDH1-WT) exhibited higher expression of TMEM158 than those with IDH1-mutant (IDH1-Mut). We also illustrated that TMEM158 mRNA expression was correlated with poor overall survival in glioma patients. Furthermore, we demonstrated that silencing TMEM158 inhibited the proliferation of glioma cells and that TMEM158 overexpression promoted the migration and invasion of glioma cells by stimulating the EMT process. We found that the underlying mechanism involves STAT3 activation mediating TMEM158-driven glioma progression. In vivo results further confirmed the inhibitory effect of the TMEM158 downregulation on glioma growth. Collectively, these findings further our understanding of the oncogenic function of TMEM158 in gliomas, which represents a potential therapeutic target, especially for GBMs.

Anti-glioma Efficacy and Mechanism of Action of Tripolinolate A from Tripolium pannonicum

Planta Medica ◽  
2018 ◽  
Vol 84 (11) ◽  
pp. 786-794
Author(s):  
Weiyun Chai ◽  
Lu Chen ◽  
Xiao-Yuan Lian ◽  
Zhizhen Zhang
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Cell Cycle Regulators ◽  
Expression Levels ◽  
Multiple Tumor ◽  
Glioma Growth

AbstractTripolinolate A as a new bioactive phenolic ester was previously isolated from a halophyte of Tripolium pannonicum. However, the in vitro and in vivo anti-glioma effects and mechanism of tripolinolate A have not been investigated. This study has demonstrated that (1) tripolinolate A inhibited the proliferation of different glioma cells with IC50 values of 7.97 to 14.02 µM and had a significant inhibitory effect on the glioma growth in U87MG xenograft nude mice, (2) tripolinolate A induced apoptosis in glioma cells by downregulating the expressions of antiapoptotic proteins and arrested glioma cell cycle at the G2/M phase by reducing the expression levels of cell cycle regulators, and (3) tripolinolate A also remarkably reduced the expression levels of several glioma metabolic enzymes and transcription factors. All data together suggested that tripolinolate A had significant in vitro and in vivo anti-glioma effects and the regulation of multiple tumor-related regulators and transcription factors might be responsible for the activities of tripolinolate A against glioma.

scholarly journals MicroRNA-139-5p Inhibits Cell Proliferation and Invasion by Targeting RHO-Associated Coiled-Coil-Containing Protein Kinase 2 in Ovarian Cancer

2018 ◽  
Vol 26 (3) ◽  
pp. 411-420 ◽  
Author(s):  
Yanli Wang ◽  
Jia Li ◽  
Chunling Xu ◽  
Xiaomeng Zhang
Keyword(s):  
Ovarian Cancer ◽  
Protein Kinase ◽  
Coiled Coil ◽  
Figo Stage ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Poor Overall Survival

Increasing evidence indicates that the dysregulation of microRNAs is associated with the development and progression of various cancers. MicroRNA-139-5p (miR-139-5p) has been reported to have a tumor suppressive role in many types of cancers. The role of miR-139-5p in ovarian cancer (OC) is poorly understood. The purpose of the present study was to explore the expression of miR-139-5p and its function in OC. The results showed that miR-139-5p expression was markedly downregulated in OC tissues and cell lines. In addition, underexpression of miR-139-5p was significantly associated with FIGO stage, lymph mode metastasis, and poor overall survival of OC patients. Functional analyses indicated that overexpression of miR-139-5p significantly inhibited proliferation, colony formation, migration, and invasion of OC cells. Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) was identified as a direct target of miR-139-5p using luciferase reporter assays, qualitative real-time reverse transcriptase PCR (qRT-PCR), and Western blot. In addition, ROCK2 expression was upregulated and was inversely correlated with miR-139-5p levels in OC tissues. Rescue experiments showed that overexpression of ROCK2 effectively reversed the inhibitory effect of OC cells induced by miR-139-5p. Most interestingly, in vivo studies indicated that miR-139-5p markedly suppressed the growth of tumors by repressing ROCK2 expression in nude mice. Taken together, these findings demonstrated that miR-139-5p plays an important tumor suppressor role in OC by directly binding to ROCK2, providing a novel target for the molecular treatment of OC.

scholarly journals The Circ_0001367/miR-545-3p/LUZP1 Axis Regulates Cell Proliferation, Migration and Invasion in Glioma Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuchen Dong ◽  
Peng Zhang ◽  
Liang Liu ◽  
Haoran Li ◽  
Shan Cheng ◽  
...  
Keyword(s):  
Leucine Zipper ◽  
Cell Function ◽  
Glioma Cells ◽  
Malignant Tumour ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function

Glioma is the most common primary intracranial malignant tumour in adults. It has a high incidence and poses a serious threat to human health. Circular RNA is a hotspot of cancer research. In this study, we aimed to explore the role of circ_0001367 in gliomagenesis and the underlying mechanism. First, qRT-PCR was conducted, which showed that circ_0001367 level was downregulated in glioma tissues and cells. Next, gain-of-function and loss-of-function assays were performed, which indicated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells. Subsequent bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation assays and cell function assays demonstrated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells by absorbing miR-545-3p and thereby regulating the expression of leucine zipper protein (LUZP1). Finally, an in vivo experiment was conducted, which demonstrated that circ_0001367 inhibited glioma growth in vivo by modulating miR-545-3p and LUZP1. Taken together, the results of this study demonstrate that the circ_0001367/miR-545-3p/LUZP1 axis may be a novel target for glioma therapy.

scholarly journals Depressive Effectiveness of Vigabatrin (y-Vinyl-GABA), an Antiepileptic Drug, in Intermediate-conductance Calcium-Activated Potassium Channels in Human Glioma Cells

2021 ◽  
Author(s):  
Te-Yu Hung ◽  
Huai-Ying Ingrid Huang ◽  
Sheng-Nan Wu ◽  
Chin-Wei Huang
Keyword(s):  
Antiepileptic Drug ◽  
Glioma Cells ◽  
Ionic Currents ◽  
Ionic Channels ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Calcium Activated Potassium Channels ◽  
Inwardly Rectifying

Abstract Background: Vigabatrin (VGB) is an approved non-traditional antiepileptic drug that has been revealed to have potential for treating brain tumors; however, its effect on ionic channels in glioma cells remains largely unclear. Methods: With the aid of patch-clamp technology, we investigated the effects of VGB on various ionic currents in the glioblastoma multiforme cell line 13-06-MG. Results: In cell-attached configuration, VGB concentration-dependently reduced the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels, while DCEBIO (5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) counteracted the VGB-induced inhibition of IKCa channels. However, the activity of neither large-conductance Ca2+-activated (BKCa) nor inwardly rectifying K+ (KIR) channels were affected by the presence of VGB in human 13-06-MG cells. However, in the continued presence of VGB, the addition of GAL-021 or BaCl2 effectively suppressed BKCa and KIR channels. Conclusions: The inhibitory effect of VGB on IKCa channels demonstrated in the current study could be an important underlying mechanism of VGB-induced antineoplastic (e.g., anti-glioma) actions.

miR-4530 inhibits the malignant biological behaviors of human glioma cells by directly targeting RTEL1

2020 ◽  
Vol 52 (12) ◽  
pp. 1394-1403
Author(s):  
Tuo Wang ◽  
Yan Zhang ◽  
Bo Cui ◽  
Maode Wang ◽  
Ya Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Nude Mice ◽  
Colony Formation ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Over Expression

Abstract Human glioma is the most common primary brain tumor and is associated with high morbidity and mortality. Aberrant expressions of microRNAs (miRNAs) are involved in glioma progression. In the present study, we aimed to elucidate the roles of miR-4530 in the pathogenesis of gliomas. miR-4530 expression was examined in human glioma clinical tissues and cell lines including U251 and T98G. The target gene of miR-4530, RTEL1, was predicted with online tools and validated by luciferase reporter assay. Lentivirus infection, transfection of plasmids, and miRNA mimics were used to manipulate gene expression. Cell proliferation was determined using the CCK-8 method, and migration and invasion assays were determined with transwell experiments. Colony formation was measured by crystal violet staining, while apoptosis was determined by Annexin V/PI staining. The anti-tumor effects of miR-4530 were evaluated in nude mice xenografted using U251 cells. Our results showed that miR-4530 was significantly down-regulated in human glioma tissues and cell lines. miR-4530 over-expression inhibited the malignant behaviors of U251 and T98G cells, including reduced proliferation, diminished colony formation, migration and invasion, and increased apoptosis. Further mechanistic investigations revealed that RTEL1 is a direct functional target of miR-4530 in gliomas, and its over-expression remarkably reverses the effects of miR-4530 mimics on inhibiting these malignant behaviors. In addition, miR-4530 over-expression inhibited the growth of xenografted U251 glioma in nude mice. Therefore, miR-4530 acts as a tumor-suppressor gene and inhibits the malignant biological behaviors of human glioma cells, which is associated with directly targeting RTEL1. The miR-4530/RTEL1 axis is a potential therapeutic target for gliomas.

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 Circ_0001367 inhibits glioma proliferation, migration and invasion by sponging miR-431 and thus regulating NRXN3

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Liang Liu ◽  
Peng Zhang ◽  
Xuchen Dong ◽  
Haoran Li ◽  
Suwen Li ◽  
...  
Keyword(s):  
Close Correlation ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Dependent Manner ◽  
Glioma Growth

AbstractMany studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.

scholarly journals Depressive Effectiveness of Vigabatrin (y-Vinyl-GABA), an Antiepileptic Drug, in Intermediate-conductance Calcium-Activated Potassium Channels in Human Glioma Cells

2020 ◽  
Author(s):  
Te-Yu Hung ◽  
Huai-Ying Ingrid Huang ◽  
Sheng-Nan Wu ◽  
Chin-Wei Huang
Keyword(s):  
Antiepileptic Drug ◽  
Glioma Cells ◽  
Ionic Currents ◽  
Ionic Channels ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Calcium Activated Potassium Channels ◽  
Inwardly Rectifying

Abstract Background: Vigabatrin (VGB) is an approved non-traditional antiepileptic drug that has been revealed to have potential for treating brain tumors; however, its effect on ionic channels in glioma cells remains largely unclear. Methods: With the aid of patch-clamp technology, we investigated the effects of VGB on various ionic currents in the glioblastoma multiforme cell line 13-06-MG. Results: In cell-attached configuration, VGB concentration-dependently reduced the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels, while DCEBIO (5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) counteracted the VGB-induced inhibition of IKCa channels. However, the activity of neither large-conductance Ca2+-activated (BKCa) nor inwardly rectifying K+ (KIR) channels were affected by the presence of VGB in human 13-06-MG cells. However, in the continued presence of VGB, the addition of GAL-021 or BaCl2 effectively suppressed BKCa and KIR channels. Conclusions: The inhibitory effect of VGB on IKCa channels demonstrated in the current study could be an important underlying mechanism of VGB-induced antineoplastic (e.g., anti-glioma) actions.

scholarly journals MicroRNA-302c enhances the chemosensitivity of human glioma cells to temozolomide by suppressing P-gp expression

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
YiHan Wu ◽  
Yuan Yao ◽  
YongLi Yun ◽  
MeiLing Wang ◽  
RunXiu Zhu
Keyword(s):  
Glioma Cells ◽  
Inverse Correlation ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Glycoprotein P ◽  
P Glycoprotein

Abstract Increasing evidence indicates that microRNAs (miRNAs) participate in the regulation of chemoresistance in a variety of cancers including glioma. However, the molecular mechanism underlying the development of chemoresistance in glioma is not well understood. The aim of the present study was to explore the role of miRNAs in the chemosensitivity of glioma cells and the underlying mechanism. By microarray and qRT-PCR, we observed significant down-regulation of microRNA-302c (miR-302c) in the temozolomide (TMZ)-resistant human glioma tissues/cells. The low expression of miR-302c was closely associated with poor prognosis and chemotherapy resistant in patients. miR-302c up-regulation re-sensitized U251MG-TMZ cells and LN229-TMZ cells to TMZ treatment, as evidenced by inhibition of the cell viability, cell migration, and invasion capacity, and promotion of the apoptosis after TMZ treatment. Furthermore, P-glycoprotein (P-gp) was identified as a functional target of miR-302c and this was validated using a luciferase reporter assay. In addition, P-gp was found to be highly expressed in U251MG-TMZ cells and there was an inverse correlation between P-gp and miR-302c expression levels in clinical glioma specimens. Most importantly, we further confirmed that overexpression of P-gp reversed the enhanced TMZ-sensitivity induced by miR-302c overexpression in U251MG-TMZ and LN229-TMZ cells. Our finding showed that up-regulation of miR-302c enhanced TMZ-sensitivity by targeting P-gp in TMZ-resistant human glioma cells, which suggests that miR-302c would be potential therapeutic targets for chemotherapy-resistant glioma patients.

scholarly journals MiR-450a-5p strengthens the drug sensitivity of gefitinib in glioma chemotherapy via regulating autophagy by targeting EGFR

Oncogene ◽  
2020 ◽  
Vol 39 (39) ◽  
pp. 6190-6202 ◽  
Author(s):  
Yu Liu ◽  
Liang Yang ◽  
Fan Liao ◽  
Wei Wang ◽  
Zhi-Fei Wang
Keyword(s):  
Signaling Pathway ◽  
Drug Sensitivity ◽  
Kinase Inhibitor ◽  
Glioma Cells ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Glioma Growth

Abstract Glioma reported to be refractory to EGFR tyrosine kinase inhibitor is the most common malignant tumor in central nervous system. Our research showed the low expression of miR-450a-5p and high expression of EGFR in glioma tissues. MiR-450a-5p was also observed to synergize with gefitinib to inhibit the proliferation, migration and invasion and induce the apoptosis and autophagy of glioma cells. Furthermore, miR-450a-5p was demonstrated to target 3′UTR of EGFR, and regulated EGFR-induced PI3K/AKT/mTOR signaling pathway. Moreover, the above effects induced by miR-450a-5p in glioma cells were reversed by WIPI1 silencing. The inhibition role of miR-450a-5p on glioma growth was also confirmed in vivo by subcutaneous and intracranial tumor xenografts. Therefore, we conclude that miR-450a-5p synergizes with gefitinib to inhibit the glioma tumorigenesis through inducing autophagy by regulating the EGFR-induced PI3K/AKT/mTOR signaling pathway, thereby enhancing the drug sensitivity of gefitinib.

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