RIT1 Promotes Glioma Proliferation and Invasion via the NF-ĸB/p65 pathway

Partially Restrained ◽

And Function ◽

Abstract RIT1, a member of the Ras family, has been identified as an oncogene in several malignancies. However, the expression and function of RIT1 in glioma remains to be addressed. In this study, we found RIT1 was upregulated in glioma and was associated with poor prognosis of glioma patients. Manipulating RIT1 levels in glioma cells via RNA interference significantly inhibited glioma cell proliferation and invasion in vitro whereas RIT1 overexpression exhibited the opposite effects. Mechanistically, we demonstrate that RIT1 engaged in the activation of the NF-ĸB pathway in vitro and in vivo. Furthermore, treating RIT1-overexpressing glioma cells with the p65 siRNA partially restrained their proliferation and invasion. Together these results indicate RIT1 contributes to the development and metastasis of glioma via the NF-ĸB pathway and suggest that targeting RIT1 may be a treatment strategy for this disease.

CircRNA Circ-ITCH Inhibits the Proliferation and Invasion of Glioma Cells Through Targeting the miR-106a-5p/SASH1 Axis

Cell Transplantation ◽

10.1177/0963689720983785 ◽

2021 ◽

Vol 30 ◽

pp. 096368972098378

Author(s):

Wei Chen ◽

Ming Wu ◽

Si-Tong Cui ◽

Yue Zheng ◽

Zhen Liu ◽

...

Keyword(s):

Cell Proliferation ◽

Glioma Cell ◽

Glioma Cells ◽

Polymerase Chain Reaction Analysis ◽

Suppressive Effect ◽

Inhibitory Effect ◽

Circ-ITCH, a novel circRNA, was generated from several exons of itchy E3 ubiquitin protein ligase (ITCH). Recently, circ-ITCH has been demonstrated to be involved in cancer development. However, there have been few investigations on the specific role of circ-ITCH in glioma. In this study, we performed quantitative real-time polymerase chain reaction analysis and identified that circ-ITCH was significantly downregulated in glioma tissues and cell lines. The function assays showed that upregulation of circ-ITCH inhibited glioma cell proliferation and invasion in vitro as well as reduced cell growth in vivo. Moreover, miR-106a-5p was found serving as a target of circ-ITCH and miR-106a-5p mimics could reverse the inhibitory effect of circ-ITCH on glioma cell proliferation and invasion. We also revealed that circ-ITCH increased SASH1 expression by sponging miR-106a-5p in glioma cells. In addition, SASH1 downregulation could abrogate the suppressive effect of circ-ITCH on glioma progression. Taken together, our results suggested that circ-ITCH could suppress glioma cell proliferation and invasion via regulating the miR-106a-5p/SASH1 axis, elucidating a novel molecular target for glioma treatment.

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

Analytical Cellular Pathology ◽

10.1155/2021/8980711 ◽

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.

MicroRNA-585 inhibits human glioma cell proliferation by directly targeting MDM2

Cancer Cell International ◽

10.1186/s12935-020-01528-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Wangsheng Chen ◽

Lan Hong ◽

Changlong Hou ◽

Yibin Wang ◽

Fei Wang ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Glioma Cell ◽

Glioma Cells ◽

Human Glioma ◽

Human Glioma Cells ◽

Human Glioma Cell ◽

Glioma Cell Proliferation

Abstract Background MicroRNAs (miRNAs) are important regulators for cancer cell proliferation. miR-585 has been shown to inhibit the proliferation of several types of cancer, however, little is known about its role in human glioma cells. Methods miR-585 levels in human glioma clinical samples and cell lines were examined by quantitative real-time PCR (qRT-PCR) analysis. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and EdU incorporation assays in vitro. For in vivo investigations, U251 cells were intracranially inoculated in BALB/c nude mice and xenografted tumors were visualized by magnetic resonance imaging (MRI). Results miR-585 expression is downregulated in human glioma tissues and cell lines compared with non-cancerous counterparts. Additionally, miR-585 overexpression inhibits and its knockdown promotes human glioma cell proliferation in vitro. Moreover, miR-585 overexpression also inhibits the growth of glioma xenografts in vivo, suggesting that miR-585 may act as a tumor suppressor to inhibit the proliferation of human glioma. Furthermore, miR-585 directly targets and decreases the expression of oncoprotein murine double minute 2 (MDM2). More importantly, the restoration of MDM2 via enforced overexpression markedly rescues miR-585 inhibitory effect on human glioma cell proliferation, thus demonstrating that targeting MDM2 is a critical mechanism by which miR-585 inhibits human glioma cell proliferation. Conclusions Our study unveils the anti-proliferative role of miR-585 in human glioma cells, and also implicates its potential application in clinical therapy.

Long Noncoding RNA H19 Promotes Proliferation and Invasion in Human Glioma Cells by Downregulating miR-152

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15178768577951 ◽

2018 ◽

Vol 26 (9) ◽

pp. 1419-1428 ◽

Cited By ~ 18

Author(s):

Lei Chen ◽

Yuhai Wang ◽

Jianqing He ◽

Chunlei Zhang ◽

Junhui Chen ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Glioma Cell ◽

Glioma Cells ◽

Human Glioma ◽

Human Glioma Cell ◽

Glioma Cell Lines ◽

miR-152 and lncRNA H19 have been frequently implicated in various cellular processes including cell proliferation, invasion, angiogenesis, and apoptosis. However, the interaction between miR-152 and H19 in glioma has never been reported. RT-qPCR was used to examine the expression of miR-152 and H19 in human glioma cell lines and normal human astrocytes (NHAs). The interaction between miR-152 and lncRNA H19 was assessed by dual-luciferase reporter assay. MTT assay and Transwell invasion assay were used to determine the proliferation and invasion of U251 and U87 cells. A xenograft tumor experiment was performed to confirm the role of H19 in vivo. The results showed that H19 expression was upregulated and miR-152 expression was downregulated in human glioma cell lines. H19 downregulation or miR-152 upregulation suppressed glioma cell proliferation and invasion in vitro. Moreover, H19 and miR-152 directly regulated each other. Furthermore, decreased miR-152 expression alleviated si-H19-induced inhibitory effects on proliferation and invasion in glioma cells. As expected, H19 silencing hindered glioma growth in vivo. Taken together, H19 promoted glioma cell proliferation and invasion by negatively regulating miR-152 expression, providing evidence for the potential application of H19 as a biomarker and therapy target for glioma.

The involvement of the circFOXM1–miR–432–Gα12 axis in glioma cell proliferation and aggressiveness

Cell Death Discovery ◽

10.1038/s41420-021-00782-9 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Yong Gong ◽

Shuai Zhang ◽

HongXin Wang ◽

Yunfeng Huang ◽

Xing Fu ◽

...

Keyword(s):

Cell Proliferation ◽

Molecular Mechanism ◽

Glioma Cell ◽

Tumour Growth ◽

Glioma Cells ◽

Inhibitory Effect ◽

Direct Target

AbstractAccumulating evidence indicates that circFOXM1 (Hsa_circ_0025033) is highly expressed in several cancers; however, the function of circFOXM1 in glioma and the molecular mechanism have not been well explored. In the present study, we found that expression of circFOXM1 was upregulated in both glioma tissues and cell lines. In addition, circFOXM1 knockdown suppressed glioma-cell proliferation, activated apoptosis in vitro, and repressed tumour growth in vivo. Moreover, we clarified that circFOXM1 binds with miR-432, which was downregulated in glioma cells. Furthermore, we indicated that Gα12, a direct target of miR-432, was highly expressed in glioma cells, and Gα12 silencing might limit the progression of glioma. Rescue assays indicated that Gα12 reversed the inhibitory effect of circFOXM1 silencing on glioma-cell tumorigenesis. In conclusion, circFOXM1 acts as a sponge of miR-432 to promote the proliferation and aggressiveness of glioma cells through the Gα12 signalling pathway.

Mesenchymal stem cell-derived exosomal microRNA-133b suppresses glioma progression via Wnt/β-catenin signaling pathway by targeting EZH2

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1446-z ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 10

Author(s):

Haiyang Xu ◽

Guifang Zhao ◽

Yu Zhang ◽

Hong Jiang ◽

Weiyao Wang ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Glioma Cell ◽

Expression Patterns ◽

Glioma Cells ◽

Invasion And Migration ◽

And Migration

Abstract Background Mesenchymal stem cells (MSCs) play a significant role in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the effects of exosomal miR-133b derived from MSCs on glioma cell behaviors. Methods Microarray-based analysis identified the differentially expressed genes (DEGs) in glioma. The expression patterns of EZH2 and miR-133b along with interaction between them were clarified in glioma. The expression of miR-133b and EZH2 in glioma cells was altered to examine their functions on cell activities. Furthermore, glioma cells were co-cultured with MSC-derived exosomes treated with miR-133b mimic or inhibitor, and EZH2-over-expressing vectors or shRNA against EZH2 to characterize their effect on proliferation, invasion, and migration of glioma cells in vitro. In vivo assays were also performed to validate the in vitro findings. Results miR-133b was downregulated while EZH2 was upregulated in glioma tissues and cells. miR-133b was found to target and negatively regulate EZH2 expression. Moreover, EZH2 silencing resulted in inhibited glioma cell proliferation, invasion, and migration. Additionally, MSC-derived exosomes containing miR-133b repressed glioma cell proliferation, invasion, and migration by inhibiting EZH2 and the Wnt/β-catenin signaling pathway. Furthermore, in vivo experiments confirmed the tumor-suppressive effects of MSC-derived exosomal miR-133b on glioma development. Conclusion Collectively, the obtained results suggested that MSC-derived exosomes carrying miR-133b could attenuate glioma development via disrupting the Wnt/β-catenin signaling pathway by inhibiting EZH2, which provides a potential treatment biomarker for glioma.

Anti-glioblastoma Activity of Kaempferol via Programmed Cell Death Induction: Involvement of Autophagy and Pyroptosis

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.614419 ◽

2020 ◽

Vol 8 ◽

Author(s):

Suqin Chen ◽

Jing Ma ◽

Liu Yang ◽

Muzhou Teng ◽

Zheng-Quan Lai ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Mitochondrial Membrane ◽

Glioma Cell ◽

Glioma Cells ◽

Edible Plants ◽

Major Nutrient ◽

Glioma Cell Proliferation

Glioblastoma is one of the most common and lethal intracranial malignant, and is still lack of ideal treatments. Kaempferol is a major nutrient found in various edible plants, which has exhibited the potential for the treatment of glioblastoma. However, the specific anti-glioma mechanism of kaempferol is yet to be studied. Herein, we aim to explore the mechanisms underlying the anti-glioma activity of kaempferol. Our results demonstrated that kaempferol suppresses glioma cell proliferation in vitro and inhibits tumor growth in vivo. Moreover, kaempferol raises ROS and decreases mitochondrial membrane potential in glioma cells. The high levels of ROS induce autophagy then ultimately trigger the pyroptosis of glioma cells. Interestingly, when we used 3-MA to inhibit autophagy, we found that the cleaved form of GSDME was also decreased, suggesting that kaempferol induces pyroptosis through regulating autophagy in glioma cells. In conclusion, this study revealed kaempferol possesses good anti-glioma activity by inducing ROS, and subsequently leads to autophagy and pyroptosis, highlighting its clinical potentials as a natural nutrient against glioblastoma.

Metastasis tumor-associated protein-2 knockdown suppresses the proliferation and invasion of human glioma cells in vitro and in vivo

Journal of Neuro-Oncology ◽

10.1007/s11060-014-1558-3 ◽

2014 ◽

Vol 120 (2) ◽

pp. 273-281 ◽

Cited By ~ 15

Author(s):

Chun-Yuan Cheng ◽

Ying-Erh Chou ◽

Chung-Po Ko ◽

Shun-Fa Yang ◽

Shu-Ching Hsieh ◽

...

Keyword(s):

Glioma Cells ◽

Human Glioma ◽

Human Glioma Cells ◽

Dickkopf-1 Inhibition Reactivates Wnt/β-Catenin Signaling in Rhabdomyosarcoma, Induces Myogenic Markers In Vitro and Impairs Tumor Cell Survival In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms222312921 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12921

Author(s):

Irina Giralt ◽

Gabriel Gallo-Oller ◽

Natalia Navarro ◽

Patricia Zarzosa ◽

Guillem Pons ◽

...

Keyword(s):

Therapeutic Potential ◽

Positive Effects ◽

Novel Therapeutic Strategies ◽

And Function ◽

Myogenic Markers ◽

First Time ◽

Dickkopf 1 ◽

The Wnt/β-catenin signaling pathway plays a pivotal role during embryogenesis and its deregulation is a key mechanism in the origin and progression of several tumors. Wnt antagonists have been described as key modulators of Wnt/β-catenin signaling in cancer, with Dickkopf-1 (DKK-1) being the most studied member of the DKK family. Although the therapeutic potential of DKK-1 inhibition has been evaluated in several diseases and malignancies, little is known in pediatric tumors. Only a few works have studied the genetic inhibition and function of DKK-1 in rhabdomyosarcoma. Here, for the first time, we report the analysis of the therapeutic potential of DKK-1 pharmaceutical inhibition in rhabdomyosarcoma, the most common soft tissue sarcoma in children. We performed DKK-1 inhibition via shRNA technology and via the chemical inhibitor WAY-2626211. Its inhibition led to β-catenin activation and the modulation of focal adhesion kinase (FAK), with positive effects on in vitro expression of myogenic markers and a reduction in proliferation and invasion. In addition, WAY-262611 was able to impair survival of tumor cells in vivo. Therefore, DKK-1 could constitute a molecular target, which could lead to novel therapeutic strategies in RMS, especially in those patients with high DKK-1 expression.

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

10.21203/rs.3.rs-415245/v1 ◽

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.