miR-433-3p Targets AJUBA to Inhibit Malignant Progression of Glioma

2021 ◽  
pp. 1-11
Author(s):  
Jing Zhang ◽  
Yihang Guo ◽  
Yanrong Ma ◽  
Lipeng Wang ◽  
Weiyuan Li ◽  
...  
Keyword(s):  
Cell Biology ◽  
Molecular Mechanisms ◽  
Biological Function ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Malignant Progression ◽  
Expression Level ◽  
Migration And Invasion ◽  
Glioma Tissue ◽  
Bioinformatics Databases

<b><i>Introduction:</i></b> Glioma is the most aggressive and malignant type of tumors among primary intracranial tumors. miR-433-3p has been verified to be correlated with the formation and progression of many types of cancers. <b><i>Methods:</i></b> In this study, the effects of miR-433-3p and AJUBA on the proliferation, migration, and invasion of glioma and the molecular mechanisms were investigated. We analyzed bioinformatics databases and conducted cell biology experiments to determine that compared with adjacent tissue and normal cells, the expression level of miR-433-3p in glioma tissue and cells was lower, while the expression level of AJUBA was higher. Overexpressing miR-433-3p could significantly inhibit the proliferation, migration, and invasion of glioma cells and promote cell apoptosis. <b><i>Results:</i></b> In addition, after overexpressing miR-433-3p and AJUBA, it was found that overexpressing AJUBA could attenuate the inhibitory effect of overexpressing miR-433-3p on the proliferation, migration, and invasion of glioma cells, which suggested that miR-433-3p regulated the biological function of glioma by downregulating AJUBA expression. <b><i>Conclusion:</i></b> These results proved that miR-433-3p could target to inhibit the expression of AJUBA, thus inhibiting the biological function and malignant progression of glioma.

scholarly journals Long non-coding RNA PVT1 indicates a poor prognosis of glioma and promotes cell proliferation and invasion via target EZH2

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Anqiang Yang ◽  
Handong Wang ◽  
Xiaobing Yang
Keyword(s):  
Cell Lines ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Human Glioma ◽  
Expression Levels ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Proliferation And Invasion

Human glioma is one of the malignant tumors of the central nervous system (CNS). Its prognosis is poor, which is due to its genetic heterogeneity and our poor understanding of its underlying molecular mechanisms. The present study aimed to assess the relationship between plasmacytoma variant translocation 1 (PVT1) and enhancer of zeste homolog 2 (EZH2), and their effects on the proliferation and invasion of glioma cells. The expression levels of PVT1 and EZH2 in human glioma tissues and cell lines were measured using quantitative RT-PCR (qRT-PCR). Then, after siRNA-PVT1 and entire PVT1 sequence vector transfection, we determined the regulation roles of PVT1 in the proliferation, apoptosis, migration, and invasion of glioma cells. We found that the expression levels of both PVT1 and EZH2 were up-regulated in human glioma tissues and cell lines, and positively correlated with glioma malignancy. And, silencing of PVT1 expression resulted in decreased proliferation, increased apoptosis, and decreased migration and invasion. In addition, exogenous PVT1 led to increased EZH2 expression and increased proliferation and induced proliferation and invasion. These data inferred that long non-coding RNA PVT1 could be served as an indicator of glioma prognosis, and PVT1–EZH2 regulatory pathway may be a novel therapeutic target for treating glioma.

scholarly journals Nobiletin Inhibits Cell Growth, Migration and Invasion, and Enhances the Anti-Cancer Effect of Gemcitabine on Pancreatic Cancer Cells

2021 ◽  
Vol 16 (4) ◽  
pp. 1934578X2110040
Author(s):  
Xiang Ren ◽  
Yuran Ma ◽  
Xiao Wang ◽  
Xuetao Xu ◽  
Panpan Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Pancreatic Cancer Cells ◽  
Underlying Mechanisms ◽  
Sphere Formation

Natural products are very promising adjuvants with a variety of biological activities. Nobiletin, a citrus polymethoxyflavone, has been shown to exert an anticancer effect in various cell lines. In this study, we investigated the effects of nobiletin on cell viability, sphere formation, migration and invasion of pancreatic cancer cells, and the underlying mechanisms. Our results demonstrate that nobiletin significantly inhibited PANC-1 cell migration and invasion, and these effects were associated with downregulation of MMP-2. We also found that nobiletin, in a low concentration, exhibited a strong inhibitory effect on sphere formation. The potential molecular mechanisms were related to significant downregulation of p-mTOR and p-STAT3. Furthermore, we found that nobiletin combined with gemcitabine synergistically inhibited PANC-1 cell viability and sphere formation. The underlying mechanisms of the synergistic inhibition on growth were associated with decreases in p-STAT3 expression. Overall, our results suggest that nobiletin may be a promising candidate for pancreatic cancer adjuvant treatment.

scholarly journals Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Regulating Epithelial–Mesenchymal Transition

2021 ◽  
Vol 11 ◽  
Author(s):  
Boli Yang ◽  
Qiuyu Chen ◽  
Changshan Wan ◽  
Siyuan Sun ◽  
Lanping Zhu ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Squamous Cell Carcinomas ◽  
Malignant Progression ◽  
Expression Level ◽  
Migration And Invasion ◽  
Control Group ◽  
Mesenchymal Transition ◽  
Esophageal Squamous Cell Carcinomas ◽  
E Cadherin

ObjectiveThis article investigates the role of Transgelin (TAGLN) in the epithelial–mesenchymal transition (EMT) of esophageal squamous cell carcinomas (ESCC) and its possible mechanism of inhibiting the invasion of these cancers.MethodsTissue specimens and clinical information of patients with ESCC were collected to analyze the relationship between Transgelin expression level and prognosis of patients with ESCC. Transgelin siRNA was used to knock down Transgelin expression. The expression of Transgelin in Eca-109 and KYSE-150 cells was overexpressed by Transgelin-overexpressing plasmid. The effects of Transgelin overexpression and knockdown on the proliferation of Eca-109 and KYSE-150 cells were examined by Transwell chamber, scratch assay, and CCK-8 cell activity assay. RT-PCR and Western blot were used to detect the effect of Transgelin overexpression or knockdown on the mRNA and protein expressions of E-cadherin and Vimentin. TCGA data were used to analyze Transgelin co-expressed genes and further study the GO and KEGG enrichment analysis results under the influence of Transgelin.ResultsThe expression of Transgelin was low in ESCC, and its expression level was positively correlated with the prognosis of patients with ESCC. The targeted Transgelin siRNA and Transgelin-overexpressing plasmid can effectively regulate the expression of Transgelin mRNA and protein in Eca-109 and KYSE-150 cells. After overexpression of Transgelin, the invasion and proliferation abilities of Eca-109 and KYSE-150 cells were significantly decreased compared with those of the control group (P &lt; 0.05). However, Transgelin knockdown could promote the proliferation, migration, and invasion of ESCC cells. The overexpression of Transgelin inhibits EMT in ESCC. With the increase of Transgelin expression in Eca-109 and KYSE-150 cells, the expression of E-cadherin increased, while the expression of Vimentin decreased, and the difference was statistically significant (P &lt; 0.05).ConclusionTransgelin can inhibit the malignant progression of ESCC by inhibiting the occurrence of EMT.

Mechanism of Ampelopsin Inhibiting Proliferation, Remove and Incursion of Colorectal Cancer Through Regulating the Expression of LncRNA ZFPM2-AS1/miR-515-5p

2021 ◽  
Vol 11 (6) ◽  
pp. 1029-1036
Author(s):  
Sheng Yuan ◽  
Dazhong Yu
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Expression Level ◽  
Migration And Invasion ◽  
Control Group ◽  
Proliferation Inhibition ◽  
Inhibition Rate ◽  
Colorectal Cancer Cells ◽  
Sw480 Cells

The incidence rate, recurrence and metastasis rate and mortality of colorectal cancer (CRC) are high. Therefore, clinical has been looking for better treatment. Ampelopsin (AMP) has obvious inhibitory effect on some tumors. However, there is no report on the effect and mechanism of AMP on rectal cancer. To investigate the effect and mechanism of AMP on the proliferation, migration and invasion of colorectal cancer cells, at first, different concentrations of Ampelopsis japonica group (10μM, 25 μM, 50 μM), control group (without AMP), pcDNA group, pcDNA-ZFPM2-AS1 group, si-NC group, si-ZFPM2-AS1 group, miR-NC group, miR-515-5p group, AMP+pcDNA group, AMP + pcDNA-ZFPM2-AS1 group were set up. Then the expression levels of miR-515-5p and ZFPM2-AS1 were detected by QRT-PCR, protein expression was detected by Western blot, cell proliferation inhibition rate was detected by MTT method, cell invasion and migration were detected by Transwell and fluorescence activity was detected by double luciferase reporter gene assay. The results show that compared with the control group, the proliferation inhibition rate of SW480 cells in different concentrations of AMP increased and the number of migration and invasion decreased significantly. Moreover, the expression levels of CyclinD1, MMP-2 and MMP-9 were significantly lower than those in the control group, while the expression of p21 was significantly increased. The expression level of miR-515-5pin SW480 cells treated with AMP was significantly increased, while the expression level of ZFPM2-AS1 was significantly decreased. Inhibition of ZFPM2-AS1 expression or miR-515-5p overexpression could inhibit the proliferation, migration and invasion of SW480 cells and then ZFPM2-AS1 overexpression reversed the inhibitory effect of AMP on the proliferation, migration and invasion of SW480 cells. Therefore, AMP affects the proliferation, migration and invasion of colorectal cancer cells by regulating the expression of lncRNA ZFPM2-AS1/miR-515-5p, which provides a new target and new idea for the prevention and treatment of colorectal cancer.

scholarly journals RNA m1A Methyltransferase TRMT6 Predicts Poorer Prognosis and Promotes Malignant Behavior in Glioma

2021 ◽  
Vol 8 ◽  
Author(s):  
Beibei Wang ◽  
Lihua Niu ◽  
Zhengyang Wang ◽  
Zhihua Zhao
Keyword(s):  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Cox Regression ◽  
Ectopic Expression ◽  
Malignant Progression ◽  
Migration And Invasion ◽  
Central Nervous System Tumor ◽  
Tumorigenesis And Progression ◽  
Public Datasets

Background: Glioma is the most prevalent central nervous system tumor in humans, and its prognosis remains unsatisfactory due to a lack of effective therapeutic targets. The ectopic expression of N1-methyladenosine (m1A) regulators is a key participant in tumorigenesis and progression. However, the m1A regulator expression status, prognostic value, and relationship with tumor clinical features in glioma remain unclear.Methods: Public datasets were used to analyze the mRNA and protein expression levels of m1A regulators. Kaplan–Meier and Cox regression analyses were performed to confirm the prognostic value of m1A regulators in glioma. Cellular experiments were conducted to verify the effect of TRMT6 on cell function. A comprehensive bioinformatics analysis was conducted to identify the potential molecular mechanisms regulated by TEMT6 in glioma.Results: We found that the dysregulation of m1A regulators was closely associated with tumorigenesis and progression in glioma. Furthermore, TRMT6 might be a powerful and independent biomarker for prognosis in glioma. Our study showed that inhibition of TRMT6 suppressed the proliferation, migration, and invasion of glioma cells. Mechanistically, TRMT6 may be involved in glioma progression by regulating cell cycle, PI3K-AKT, TGF-beta, MTORC1, NOTCH, and MYC pathways.Conclusions: Variation in m1A regulators was closely associated with malignant progression in glioma. Silencing TRMT6 suppressed the cell proliferation, migration, and invasion in glioma. m1A regulators, especially TRMT6, might play an essential role in the malignant progression of glioma.

scholarly journals miR-139-5p Inhibits Lung Adenocarcinoma Cell Proliferation, Migration, and Invasion by Targeting MAD2L1

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jianfeng Li ◽  
Xi He ◽  
Xiaotang Wu ◽  
Xiaohui Liu ◽  
Yixiong Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Differential Analysis ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
Mirna Expression Data

Background. miR-139-5p is lowly expressed in various human cancers and exerts its antitumor effect through different molecular mechanisms, yet the molecular mechanism of miR-139-5p in lung adenocarcinoma (LUAD) remains to be further elucidated. The study is aimed at investigating the role and the regulatory mechanism of miR-139-5p in LUAD progression. Methods. Differential analysis was performed on miRNA expression data in the TCGA-LUAD dataset. qRT-PCR was employed to detect the transcription levels of miR-139-5p and MAD2L1 in LUAD cells, while western blot was carried out for the detection of MAD2L1 protein expression. CCK-8 and Transwell assays were implemented to assess LUAD cell proliferation, migration, and invasion. A dual-luciferase reporter gene assay was conducted to verify the direct targeting relationship between miR-139-5p and MAD2L1. Results. miR-139-5p was significantly downregulated in LUAD cells in comparison with that in human normal bronchial epithelial cells. Overexpressing miR-139-5p inhibited LUAD cell proliferation, migration, and invasion, while opposite results could be observed when miR-139-5p was inhibited. MAD2L1 was identified as a direct target of miR-139-5p in LUAD. Besides, the inhibitory effect of miR-139-5p overexpression on LUAD cell proliferation, migration, and invasion was attenuated by overexpressing MAD2L1. Conclusion. Our study suggests that miR-139-5p is lowly expressed in LUAD cells and inhibits LUAD cell proliferation, migration, and invasion by targeted suppressing MAD2L1 expression. It is of potential significance for the prognosis and treatment of LUAD.

scholarly journals LncRNA LINC00152 promotes laryngeal cancer progression by sponging miR-613

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 240-248 ◽  
Author(s):  
Xuesong Zheng ◽  
Su Dong ◽  
Lele Sun ◽  
Jialu Xu ◽  
Jia Liu ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Clinical Stage ◽  
Cell Cancer ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Advanced Clinical Stage ◽  
Normal Tissues

AbstractBackgroundLong noncoding RNA (lncRNA) LINC00152 (CYTOR) has been reported to be upregulated and to serve as a diagnostic biomarker in multiple types of cancers, including laryngeal squamous cell cancer (LSCC). However, the functional role and molecular mechanisms of LINC00152 in LSCC progression need to be further investigated.MethodsLINC00152 levels in LSCC and adjacent normal tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Gene knockdown of LINC00152 was achieved in LSCC cells by use of small interfering RNA (siRNA). Cell proliferation, apoptosis, migration and invasion were examined by a series of methods. The micoRNA (miRNA) interaction with LINC00152 was screened by starBase v2.0 and confirmed by luciferase reporter activity.ResultsLINC00152 levels in LSCC tissues were significantly higher than those in adjacent normal tissue, and patients with lymph node metastasis or an advanced clinical stage displayed higher LINC00152 expression. Moreover, siRNA-mediated LINC00152 knockdown significantly inhibited the proliferation, migration and invasion of LSCC cells and induced apoptosis in those cells. Mechanistically, LINC00152 functioned as a competing endogenous RNA (ceRNA) sponging miR-613. The inhibitory effect of LINC00152 knockdown on malignant behavior was abrogated by inhibiting miR-613.ConclusionLINC00152 exerts an oncogenic effect on the tumorigenesis of LSCC by sponging miR-613 and may serve as a potential target for treating LSCC.

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 LRIG1 regulates invasion and migration of human gliomas through SNAI2 and E-cadherin

2020 ◽  
Author(s):  
Xiang Tao ◽  
Wenfei Zhang ◽  
Junhui Liu ◽  
Xiaonan Zhu ◽  
Baowei Ji ◽  
...  
Keyword(s):  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Scratch Test ◽  
Inhibitory Effect ◽  
Human Gliomas ◽  
Glioma Tissue ◽  
Glioma Invasion ◽  
Invasion And Migration ◽  
And Migration ◽  
E Cadherin

Abstract The particular molecular mechanisms that activates invasion and migration of human gliomas remains obscure. Our previous study has indicated the function of leucine-rich repeats and immunoglobulin-like domains 1(LRIG1) in the inhibition of the cell invasion and downstream genes snail homolog 2(SNAI2) and E-cadherin were involved in this process. In this study we give an insight into the role SNAI2 and E-cadherin played in this process and the relationship between them in glioma tissue specimen. We employed a full length expression plasmid to overexpress LRIG1 in the malignant glioma cell line U251. Introduction of exogenous LRIG1 into U251 significantly inhibited cell invasion and metastasis detected by transwell assay and scratch test, respectively. On the other hand, LRIG1 overexpression leads to reduced SNAI2 expression and elevated E-cadherin expression, manifested by qRT-PCR and western blot, which was consistent with the results in glioma tissue specimens. Further research revealed that 4-chloro-DL-phenylalanine (PCPA), a small molecule inhibitor of SNAI2, can significantly promote the inhibitory effect of cell invasion and migration caused by overexpressed LRIG1. Our data suggested that LRIG1 as a tumor suppressor restricted glioma invasion and migration by regulating SNAI2 and E-cadherin axis and low expression of LRIG1 is associated with poor prognosis in glioma. In conclusion, restoration of LRIG1 in glioma cells could be a novel therapeutic strategy.

scholarly journals SNAP25 Inhibits Glioma Progression by Regulating Synapse Plasticity via GLS-Mediated Glutaminolysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiongzhen Huang ◽  
Changlin Lian ◽  
Yaoyuan Dong ◽  
Huijun Zeng ◽  
Boyang Liu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Glioma Cells ◽  
Glutamine Metabolism ◽  
Expression Level ◽  
Migration And Invasion ◽  
Low Grade ◽  
Data Set ◽  
Mouse Xenograft Model ◽  
Genome Atlas ◽  
Glioma Progression

BackgroundNeuronal activity regulated by synaptic communication exerts an important role in tumorigenesis and progression in brain tumors. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function ‘vesicle’ about synaptic connectivity were identified, and synaptosomal-associated protein 25 (SNAP25), one of those proteins, was found to have discrepant expression levels in neuropathies. However, the specific mechanism and prognostic value of SNAP25 during glioma progression remain unclear.MethodsUsing RNA sequencing data from The Cancer Genome Atlas (TCGA) database, the differential synaptosis-related genes between low grade glioma (LGG) and glioblastoma (GBM) were identified as highly correlated. Cox proportional hazards regression analysis and survival analysis were used to differentiate the outcome of low- and high-risk patients, and the Chinese Glioma Genome Atlas (CGGA) cohort was used for validation of the data set. RT-qPCR, western blot, and immunohistochemistry assays were performed to examine the expression level of SNAP25 in glioma cells and samples. Functional assays were performed to identify the effects of SNAP25 knockdown and overexpression on cell viability, migration, and invasion. Liquid chromatography-high resolution mass spectrometry (LC-MS)-based metabolomics approach was presented for identifying crucial metabolic disturbances in glioma cells. In situ mouse xenograft model was used to investigate the role of SNAP25 in vivo. Then, an immunofluorescence assay of the xenograft tissue was applied to evaluate the expression of the neuronal dendron formation marker-Microtubule Associated Protein 2 (MAP2).ResultsSNAP25 was decreased in level of expression in glioma tissues and cell lines, and low-level SNAP25 indicated an unfavorable prognosis of glioma patients. SNAP25 inhibited cell proliferation, migration, invasion and fostered glutamine metabolism of glioma cells, exerting a tumor suppressor role. Overexpressed SNAP25 exerted a lower expression level of MAP2, indicating poor neuronal plasticity and connectivity. SNAP25 could regulate glutaminase (GLS)-mediated glutaminolysis, and GLS knockdown could rescue the anti-tumor effect of SNAP25 in glioma cells. Moreover, upregulated SNAP25 also decreased tumor volume and prolonged the overall survival (OS) of the xenograft mouse.ConclusionSNAP25, a tumor suppressor inhibited carcinogenesis of glioma via limiting glutamate metabolism by regulating GLS expression, as well as inhibiting dendritic formation, which could be considered as a novel molecular therapeutic target for glioma.

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