scholarly journals MiR-30c Plays Diagnostic and Prognostic Roles and Mediates Epithelial–mesenchymal Transition (EMT) and Proliferation of Glioma by Affecting Notch1

2021 ◽  
Author(s):  
Mengkao Li ◽  
Wenzhi Liu ◽  
Jin Xu
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Glioma Cells ◽  
Suppressor Gene ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Normal Brain ◽  
Who Grade ◽  
Mesenchymal Transition

Abstract miR-30c functions as a tumor suppressor gene in the majority of tumors, including glioma. In our study, we discovered that the expression levels of miR-30c in glioma tissues and plasma prior to operation were lower than that in normal brain tissue following brain injury decompression and plasma in healthy volunteers. The low expression of miR-30c was closely aligned with WHO grade, tumor size, PFS, and OS. Additionally, the miR-30c expression level of tumor tissue was positively correlated with the levels found in preoperative plasma. In cell biology experiments, miR-30c was discovered to inhibit EMT, proliferation, migration, and the invasion of glioma cells. The database of miRNAs target genes, real-time quantitative PCR, western blot, and dual luciferase reporter assay demonstrated that Notch1 is the direct target gene of miR-30c. The inhibitor and shRNA-Notch1 were cotransfected into glioma cells, which illustrated that shRNA-Notch1 could reduce the enhancement of inhibitors in EMT, proliferation, migration, and the invasion of glioma cells. Therefore, we believe that when utilized as a tumor suppressor gene, miR-23a can inhibit EMT, proliferation, migration, and invasion of glioma cells by directly acting on Notch1 at the post-transcriptional level, and it is a potential diagnostic and prognostic marker.

scholarly journals Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 921-931
Author(s):  
Juan Zhao ◽  
Xue-Bin Zeng ◽  
Hong-Yan Zhang ◽  
Jie-Wei Xiang ◽  
Yu-Song Liu
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Glioma Cells ◽  
Suppressor Gene ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractLong non-coding RNA forkhead box D2 adjacent opposite strand RNA 1 (FOXD2-AS1) has emerged as a potential oncogene in several tumors. However, its biological function and potential regulatory mechanism in glioma have not been fully investigated to date. In the present study, RT-qPCR was conducted to detect the levels of FOXD2-AS1 and microRNA (miR)-506-5p, and western blot assays were performed to measure the expression of CDK2, cyclinE1, P21, matrix metalloproteinase (MMP)7, MMP9, N-cadherin, E-cadherin and vimentin in glioma cells. A luciferase reporter assay was performed to verify the direct targeting of miR-506-5p by FOXD2-AS1. Subsequently, cell viability was analyzed using the CCK-8 assay. Cell migration and invasion were analyzed using Transwell and wound healing assays, respectively. The results demonstrated that FOXD2-AS1 was significantly overexpressed in glioma cells, particularly in U251 cells. Knockdown of FOXD2-AS1 in glioma cells significantly inhibited cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) and regulated the expression of CDK2, cyclinE1, P21, MMP7 and MMP9. Next, a possible mechanism for these results was explored, and it was observed that FOXD2-AS1 binds to and negatively regulates miR-506-5p, which is known to be a tumor-suppressor gene in certain human cancer types. Furthermore, overexpression of miR-506-5p significantly inhibited cell proliferation, migration, invasion and EMT, and these effects could be reversed by transfecting FOXD2-AS1 into the cells. In conclusion, our data suggested that FOXD2-AS1 contributed to glioma proliferation, metastasis and EMT via competitively binding to miR-506-5p. FOXD2-AS1 may be a promising target for therapy in patients with glioma.

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.

Wt1-expressing progenitors contribute to multiple tissues in the developing lung

2013 ◽  
Vol 305 (4) ◽  
pp. L322-L332 ◽  
Author(s):  
Elena Cano ◽  
Rita Carmona ◽  
Ramón Muñoz-Chápuli
Keyword(s):  
Smooth Muscle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Fluorescent Protein ◽  
Wilms Tumor ◽  
Yellow Fluorescent Protein ◽  
Suppressor Gene ◽  
Differentiation Potential ◽  
Mesenchymal Transition ◽  
Lung Morphogenesis

Lungs develop from paired endodermal outgrowths surrounded by a mesodermal mesenchyme. Part of this mesenchyme arises from epithelial-mesenchymal transition of the mesothelium that lines the pulmonary buds. Previous studies have shown that this mesothelium-derived mesenchyme contributes to the smooth muscle of the pulmonary vessels, but its significance for lung morphogenesis and its developmental fate are still little known. We have studied this issue using the transgenic mouse model mWt1/IRES/GFP-Cre (Wt1cre) crossed with the Rosa26R-EYFP reporter mouse. In the developing lungs, Wt1, the Wilms' tumor suppressor gene, is specifically expressed in the embryonic mesothelium. In the embryos obtained from the crossbreeding, the Wt1-expressing cell lineage produces the yellow fluorescent protein (YFP), allowing for colocalization with differentiation markers. Wt1cre-YFP cells were very abundant from the origin of the lung buds to postnatal stages, contributing significantly to pulmonary endothelial and smooth muscle cells, bronchial musculature, tracheal and bronchial cartilage, as well as CD34+ fibroblast-like interstitial cells. Thus Wt1cre-YFP mesenchymal cells show the very same differentiation potential as the splanchnopleural mesenchyme surrounding the lung buds. FSP1+ fibroblast-like cells were always YFP−; they expressed the common leukocyte antigen CD45 and were apparently recruited from circulating progenitors. We have also found defects in pulmonary development in Wt1−/− embryos, which showed abnormally fused lung lobes, round-shaped and reduced pleural cavities, and diaphragmatic hernia. Our results suggest a novel role for the embryonic mesothelium-derived cells in lung morphogenesis and involve the Wilms' tumor suppressor gene in the development of this organ.

scholarly journals Neutron activation increases activity of ruthenium-based complexes and induces cell death in glioma cells independent of p53 tumor suppressor gene

BioMetals ◽  
2017 ◽  
Vol 30 (2) ◽  
pp. 295-305 ◽  
Author(s):  
Aline Monezi Montel ◽  
Raquel Gouvêa dos Santos ◽  
Pryscila Rodrigues da Costa ◽  
Elisângela de Paula Silveira-Lacerda ◽  
Alzir Azevedo Batista ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Suppressor ◽  
Neutron Activation ◽  
Tumor Suppressor Gene ◽  
Glioma Cells ◽  
Suppressor Gene ◽  
P53 Tumor Suppressor ◽  
P53 Tumor Suppressor Gene

scholarly journals DLC1 tumor suppressor gene inhibits migration and invasion of multiple myeloma cells through RhoA GTPase pathway

Leukemia ◽  
2008 ◽  
Vol 23 (2) ◽  
pp. 383-390 ◽  
Author(s):  
V Ullmannova-Benson ◽  
M Guan ◽  
X Zhou ◽  
V Tripathi ◽  
X-Y Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Myeloma Cells ◽  
Rhoa Gtpase

scholarly journals MicroRNA-361-5p Inhibits Tumorigenesis and the EMT of HCC by Targeting Twist1

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Liang-Chun Yin ◽  
Gang Xiao ◽  
Rui Zhou ◽  
Xiao-Ping Huang ◽  
Ning-Lei Li ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Suppressive Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Bioinformatics Analyses ◽  
Mesenchymal Transition ◽  
Reporter Assays

MicroRNA-361-5p (miR-361-5p) is a tumor suppressor miRNA that is dysregulated in several types of human cancer. However, the functional significance of miR-361-5p in hepatocellular carcinoma (HCC) is unclear. This study explored the biological function of miR-361-5p in regulating the progression of HCC and the underlying molecular mechanism. RT-qPCR analysis showed that miR-361-5p was downregulated in HCC tissues and cell lines. Functional analysis revealed that miR-361-5p acted as a tumor suppressor, inhibiting cell proliferation, migration, and invasion in HCC cell lines. Bioinformatics analyses identified Twist1 as a direct target of miR-361-5p, which was validated by dual-luciferase reporter assays, RT-qPCR, and western blotting. Rescue experiments indicated that Twist1 may mediate the tumor-suppressive effect of miR-361-5p in HCC cells, and this was supported by the effect of miR-361-5p on inhibiting the epithelial-mesenchymal transition (EMT) by targeting Twist1. This study is the first to suggest that miR-361-5p inhibits tumorigenesis and EMT in HCC by targeting Twist1. These findings are valuable for the diagnosis and clinical management of HCC.

scholarly journals Knockdown lncRNA DLEU1 Inhibits Gliomas Progression and Promotes Temozolomide Chemosensitivity by Regulating Autophagy

2020 ◽  
Vol 11 ◽  
Author(s):  
Qiao-Li Lv ◽  
Li-Chong Wang ◽  
Dang-Chi Li ◽  
Qian-Xia Lin ◽  
Xiao-Li Shen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Normal Brain ◽  
Mesenchymal Transition ◽  
Cycle Arrest ◽  
Underlying Mechanisms ◽  
Multiple Drugs ◽  
Emt Markers ◽  
Brain Tissues

Gliomas are the most fatal malignant cerebral tumors. Temozolomide (TMZ), as the primary chemotherapy drug, has been widely used in clinics. However, resistance of TMZ still remains to poor defined. LncRNAs have been reported to play crucial roles in progression of various cancers and resistance of multiple drugs. However, the biological function and underlying mechanisms of most lncRNAs in glioma still remains unclear. Based on the TCGA database, a total of 94 differentially expressed lncRNAs, including 16 up-regulated genes and 78 downregulated genes were identified between gliomas and normal brain tissues. Subsequently, lncRNA DLEU1, HOTAIR, and LOC00132111 were tested to be significantly related to overall survival (OS) between high- and low-expression groups. Additionally, we verified that lncRNA DLEU1 was high expressed in 108 gliomas, compared with 19 normal brain tissues. And high expression of lncRNA DLEU1 predicted a poor prognosis (HR = 1.703, 95%CI: 1.133–2.917, p-value = 0.0159). Moreover, functional assays revealed that knockdown of lncRNA DLEU1 could suppress the proliferation by inducing cell cycle arrest at G1 phase and reducing the S phase by down-regulating the CyclinD1 and p-AKT, as the well as migration and invasion by inhibiting the epithelial–mesenchymal transition (EMT) markers, such as ZEB1, N-cadherin, β-catenin and snail in glioma cells. Furthermore, silencing lncRNA DLEU1 suppressed TMZ-activated autophagy via regulating the expression of P62 and LC3, and promoted sensitivity of glioma cells to TMZ by triggering apoptosis. Conclusively, our study indicated that lncRNA DLEU1 might perform as a prognostic potential target and underlying therapeutic target for sensitivity of glioma to TMZ.

scholarly journals Epigenetics of SFRP1: The Dual Roles in Human Cancers

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 445 ◽  
Author(s):  
Rashidah Baharudin ◽  
Francis Yew Fu Tieng ◽  
Learn-Han Lee ◽  
Nurul Syakima Ab Mutalib
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Treatment Resistance ◽  
Suppressor Gene ◽  
Tumor Promoter ◽  
Migration And Invasion ◽  
Future Research ◽  
Dual Roles ◽  
Human Cancers ◽  
Sfrp1 Expression

Secreted frizzled-related protein 1 (SFRP1) is a gene that belongs to the secreted glycoprotein SFRP family. SFRP1 has been classified as a tumor suppressor gene due to the loss of expression in various human cancers, which is mainly attributed by epigenetic inactivation via DNA methylation or transcriptional silencing by microRNAs. Epigenetic silencing of SFRP1 may cause dysregulation of cell proliferation, migration, and invasion, which lead to cancer cells formation, disease progression, poor prognosis, and treatment resistance. Hence, restoration of SFRP1 expression via demethylating drugs or over-expression experiments opens the possibility for new cancer therapy approach. While the role of SFRP1 as a tumor suppressor gene is well-established, some studies also reported the possible oncogenic properties of SFRP1 in cancers. In this review, we discussed in great detail the dual roles of SFRP1 in cancers—as tumor suppressor and tumor promoter. The epigenetic regulation of SFRP1 expression will also be underscored with additional emphasis on the potentials of SFRP1 in modulating responses toward chemotherapeutic and epigenetic-modifying drugs, which may encourage the development of novel drugs for cancer treatment. We also present findings from clinical trials and patents involving SFRP1 to illustrate its clinical utility, extensiveness of each research area, and progression toward commercialization. Lastly, this review provides directions for future research to advance SFRP1 as a promising cancer biomarker.

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