scholarly journals Overexpression of RAB34 Associates With Tumor Aggressiveness and Immune Infiltration in Glioma

2021 ◽  
Author(s):  
Peng Hou ◽  
Quan Wan ◽  
Qing Wang ◽  
Xuechao Wu ◽  
Xiaojie Lu
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Migration And Invasion ◽  
Rna Seq ◽  
Clinical Value ◽  
Mesenchymal Transition ◽  
Immune Infiltration ◽  
Genome Atlas

Abstract Background: RAB34 is aberrantly expressed in various cancers and exhibits oncogenic properties. However, its function in glioma remains largely unclear. Herein, we investigated the clinical value and biological functions of RAB34 in glioma.Methods: In this study, we collected 697 RNA-seq data from The Cancer Genome Atlas (TCGA) dataset and 325 RNA-seq data from Chinese Glioma Genome Atlas (CGGA) dataset. CCK-8 and EdU assays were employed to assess cell proliferation ability. The transwell assay was utilized to explore cell migration and invasion capacities. Western blot coupled with qRT-PCR were employed to determine the protein, as well as RNA contents. The statistical analyses along with the graphical work were mainly implemented in the R software.Results: RAB34 expression was positively related to the glioma tumor grade, and predicted poor outcomes for glioma patients. RAB34 expression was significantly upregulated in classical and mesenchymal subtypes, and IDH wild-type gliomas. Additionally, RAB34 expression was regulated by promoter DNA methylation. Moreover, RAB34 expression was remarkably correlated with inflammatory activities, immune infiltration, and immune checkpoints in glioma. In vitro experiments demonstrated that inhibition of RAB34 restrained the growth, migration, as well as invasion of glioma cells, and reversed the epithelial-to-mesenchymal transition (EMT) process. Conclusion: Our findings established RAB34 as a novel progression-related biomarker and a possible immunotherapy target for glioma.

scholarly journals Overexpression of RAB34 associates with tumor aggressiveness and immune infiltration in glioma

2021 ◽  
Author(s):  
Peng Hou ◽  
Quan Wan ◽  
Qing Wang ◽  
Xuechao Wu ◽  
Xiaojie Lu
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Migration And Invasion ◽  
Rna Seq ◽  
Clinical Value ◽  
Mesenchymal Transition ◽  
Immune Infiltration ◽  
Genome Atlas

Abstract Background RAB34 is aberrantly expressed in various cancers and exhibits oncogenic properties. However, its function in glioma remains largely unclear. Herein, we investigated the clinical value and biological functions of RAB34 in glioma. Methods In this study, we collected 697 RNA-seq data from The Cancer Genome Atlas (TCGA) dataset and 325 RNA-seq data from Chinese Glioma Genome Atlas (CGGA) dataset. CCK-8 and EdU assays were employed to assess cell proliferation ability. The transwell assay was utilized to explore cell migration and invasion capacities. Western blot coupled with qRT-PCR were employed to determine the protein, as well as RNA contents. The statistical analyses along with the graphical work were mainly implemented in the R software. Results RAB34 expression was positively related to the glioma tumor grade, and predicted poor outcomes for glioma patients. RAB34 expression was significantly upregulated in classical and mesenchymal subtypes, and IDH wild-type gliomas. Additionally, RAB34 expression was regulated by promoter DNA methylation. Moreover, RAB34 expression was remarkably correlated with inflammatory activities, immune infiltration, and immune checkpoints in glioma. In vitro experiments demonstrated that inhibition of RAB34 restrained the growth, migration, as well as invasion of glioma cells, and reversed the epithelial-to-mesenchymal transition (EMT) process. Conclusion Our findings established RAB34 as a novel progression-related biomarker and a possible immunotherapy target for glioma.

scholarly journals MiR-1301-3p Inhibits Epithelial to Mesenchymal Transition via Targeting RhoA in Pancreatic Cancer

2020 ◽  
Author(s):  
Xinxue Zhang ◽  
Xin Zhao ◽  
Junming Xu ◽  
Jun Ma ◽  
Zhe Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Pathological Differentiation

Abstract Background: Micro(mi)RNAs play an essential role in the epithelial-mesenchymal transition (EMT) process in human cancers. This study aimed to uncover the regulatory mechanism of miR-1301-3p on EMT in pancreatic cancer (PC).Methods: GEO database (GSE31568, GSE41372, and GSE32688) and the PC cohort of The Cancer Genome Atlas were applied to discover the expression and prognostic role of miR-1301-3p. In the validation cohort, qRT-PCR was performed in 72 paired PC tissue samples. CCK-8, wound healing, and transwell migration assays were used to detect miR-1301-3p function on PC cells. Luciferase reporter assays and western blotting were performed to discover the potential target of miR-1301-3p on EMT.Results: Our study revealed that miR-1301-3p was downregulated in PC tissues compared with normal samples. A low level of miR-1301-3p was associated with malignant pathological differentiation, lymphatic metastasis, tumor residual, and unsatisfactory overall survival. Gene Ontology analyses indicated that miR-1301-3p possibly regulated cell cycle and adheren junction. In vitro assays showed that miR-1301-3p suppressed proliferation, migration, and invasion ability of PC cells. Mechanically, miR-1301-3p inhibits RhoA expression, and knockdown of RhoA upregulated E-cadherin; however, downregulated N-cadherin and vimentin level.Conclusions: MiR-1301-3p acts as a prognostic biomarker for PC and inhibits PC progression by targeting RhoA induced EMT process.

scholarly journals Knockdown long noncoding RNA SLC8A1-AS1 attenuate cell invasion and migration in glioma via suppression of Wnt-β catenin signaling pathways

2020 ◽  
Author(s):  
Ling He ◽  
Hui Yang ◽  
Xiao-long Zhu ◽  
Yan Zhang ◽  
Kun Lv
Keyword(s):  
Noncoding Rna ◽  
Epithelial To Mesenchymal Transition ◽  
Glioma Cells ◽  
Neural System ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Validation Experiment

Abstract Background: Glioma, as the most common aggressive malignant tumor in the central nervous system, is still an insurmountable disease in neural system. The potential mechanism of its carcinogenesis remains largely unclear. Methods: In the present study, we identified dysregulated lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1-AS1) as associated with glioma based on The Cancer Genome Atlas （TCGA）data. Validation experiment was conducted to confirm a high expression level of lncRNA SLC8A1-AS1 in glioma tissues. Results: Down-regulation of lncRNA SLC8A1-AS1 suppressed proliferation, clone formation, migration and invasion of glioma cells in vitro and in vivo. Moreover, lncRNA SLC8A1-AS1 silencing decreased the activity of the Wnt/β-catenin pathway and suppressed the epithelial to mesenchymal transition (EMT) in glioma cells. Conclusions: Collectively, these findings provide a novel insights into the function and mechanism of lncRNA SLC8A1-AS1 in the pathogenesis of glioma and highlight its potential as a therapeutic target for glioma intervention.

scholarly journals Knockdown long noncoding RNA SLC8A1-AS1 attenuate cell invasion and migration in glioma via suppression of Wnt-β catenin signaling pathways

2020 ◽  
Author(s):  
Ling He ◽  
Hui Yang ◽  
Xiao-long Zhu ◽  
Yan Zhang ◽  
Kun Lv
Keyword(s):  
Noncoding Rna ◽  
Epithelial To Mesenchymal Transition ◽  
Glioma Cells ◽  
Neural System ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Validation Experiment

Abstract Background Glioma, as the most common aggressive malignant tumor in the central nervous system, is still an insurmountable disease in neural system. The potential mechanism of its carcinogenesis remains largely unclear. Methods In the present study, we identified dysregulated lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1-AS1) as associated with glioma based on The Cancer Genome Atlas (TCGA)data. Validation experiment was conducted to confirm a high expression level of lncRNA SLC8A1-AS1 in glioma tissues. Results Down-regulation of lncRNA SLC8A1-AS1 suppressed proliferation, clone formation, migration and invasion of glioma cells in vitro and in vivo. Moreover, lncRNA SLC8A1-AS1 silencing decreased the activity of the Wnt/β-catenin pathway and suppressed the epithelial to mesenchymal transition (EMT) in glioma cells. Conclusions Collectively, these findings provide a novel insights into the function and mechanism of lncRNA SLC8A1-AS1 in the pathogenesis of glioma and highlight its potential as a therapeutic target for glioma intervention.

scholarly journals Potential Role of microRNA-183 as a Tumor Suppressor in Hepatocellular Carcinoma

2018 ◽  
Vol 51 (5) ◽  
pp. 2065-2072 ◽  
Author(s):  
Wei Bian ◽  
Hongfei Zhang ◽  
Miao Tang ◽  
Shaojun Zhang ◽  
Lichao Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Reporter Assays

Background/Aims: Disseminated tumors, known as metastases, are responsible for ninety-percent of mortality due to cancer. Epithelial to mesenchymal transition, a phenomenon required for morphological conversion of non-motile discoid shaped epithelial cells to highly motile spindle-shaped mesenchymal cells, is thought to be a pre-requisite for metastatic progression. Metastasis-associated 1 (MTA1) protein is a prime inducer of EMT and metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the molecular mechanisms that regulate the expression and function of MTA1 in HCC have not been elucidated. Methods: In silico prediction algorithms were used to find microRNAs (miRNAs) that may target MTA1. We examined the relationship between the expression of MTA1 and miR-183 using quantitative real time PCR. We also determined the levels of the MTA1 protein using immunohistochemistry. Reporter assays, in the presence and absence of the miR-183 mimic, were used to confirm MTA1 as a bona fide target of miR183. The effect of miR-183 on HCC pathogenesis was determined using a combination of in vitro migration and invasion assay, together with in vivo xenograft experiments. The correlation between miR-183 and MTA1 expression was also studied in samples from HCC patients, and in The Cancer Genome Atlas dataset. Results: Analysis of the sequence database revealed that MTA1 is a putative target of miR-183. MTA1 protein and RNA expression showed opposite trends to miR-183 expression in breast, renal, prostate, and testicular tissue samples from cancer patients, and in the metastatic HCC cell line HepG2. An inverse correlation was also observed between MTA1 (high) and miR-183 (low) expression within samples from HHC patients and in the TCGA dataset. Reporter assays in HepG2 cells showed that miR-183 could inhibit translation of a reporter harboring the wild-type, but not the mutant miR-183 3’-untranslated region (UTR). In addition, miR-183 significantly inhibited in vitro migration and invasion in HepG2 cells, and in vivo hepatic metastasis. Conclusion: Our results reveal a novel post-transcriptional regulatory mechanism for MTA1 expression via miR-183, which is suppressed during HCC pathogenesis.

(S,R)3-(4-Hydroxyphenyl)-4,5-Dihydro-5-Isoxazole Acetic Acid Methyl Ester Inhibits Epithelial-to-Mesenchymal Transition through TGF-β/Smad4 Axis in Nasopharyngeal Carcinoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Qibing Chen ◽  
Yan Wang ◽  
Fen Li ◽  
Xiang Cheng ◽  
Yu Xiao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Nasopharyngeal Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Immunofluorescence Assay ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background: Macrophage migration inhibitory factor (MIF), originally reported as an inflammation regulating molecule, is elevated in various cancer cells, which may promote carcinogenesis. Meanwhile, ISO-1 is a potent small molecular inhibitor of MIF, which has not been investigated in nasopharyngeal carcinoma (NPC); hence the impact of ISO-1 on NPC cells remains to be illustrated. Objective: This study intended to explore the biological function of ISO-1 in NPC cells in vitro and prove a possibility of ISO-1 being a novel agent in NPC treatments. Methods: Gene expression of MIF in Head and Neck squamous cell carcinoma were obtained from The Cancer Genome Atlas (TCGA) database. Nasal pharyngeal tissues were collected from adult patients undergoing nasopharyngeal biopsy for MIF level detection. Proliferation of NPC cell lines 5-8B and 6-10B was studied using Cell Counting Kit-8 (CCK-8) assay and plate-colony-formation assay, apoptosis was determined by flow cytometry and TUNEL staining, migration and invasion capacities were measured by wound-healing assay and transwell assay, all to explore the function of ISO-1 in NPC cells in vitro. Epithelial-to-mesenchymal transition (EMT) level of NPC cells was determined by Western blot analysis and immunofluorescence assay. Results: Transcript level of MIF was significantly higher in head and neck squamous cell carcinoma. Protein MIF was overexpressed in human NPC tissues compared to non-cancerous ones, and its expression could be compromised by ISO-1 in vitro. 100μM ISO-1 significantly hindered NPC cells migration and invasion capacities in vitro but acted relatively poorly on proliferation and apoptosis. Immunofluorescence assay and Western blotting implied a down-regulated EMT level through TGF-β/Smad4 axis in ISO-1 treated NPC cells compared to the vehicle. Conclusion: This study indicated that MIF antagonist ISO-1 holds impact on NPC progression by influencing the migration and invasion of NPC cells ISO-1 inhibits the EMT process of NPC cells through TGF-β/Smad4 axis, supporting that prudent application of ISO-1 may be a potential adjuvant treatment for NPC.

scholarly journals FXR silencing in human colon cancer by DNA methylation and KRAS signaling

2014 ◽  
Vol 306 (1) ◽  
pp. G48-G58 ◽  
Author(s):  
Ann M. Bailey ◽  
Le Zhan ◽  
Dipen Maru ◽  
Imad Shureiqi ◽  
Curtis R. Pickering ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Colon Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Human Colon ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue ( n = 238), polyps ( n = 32), and adenocarcinomas, staged I–IV ( n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ∼12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

scholarly journals CircMTO1 suppresses hepatocellular carcinoma progression via the miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling pathway and epithelial-to-mesenchymal transition

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Dandan Li ◽  
Jiawei Zhang ◽  
Jing Yang ◽  
Jie Wang ◽  
Runling Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Epithelial To Mesenchymal Transition ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
Mesenchymal Transition

AbstractCircRNA mitochondrial tRNA translation optimization 1 (circMTO1) functions as a tumor suppressor usually and is related to the progression of many tumors, including hepatocellular carcinoma (HCC). CircMTO1 is downregulated in HCC as compared to adjacent nontumor tissue, which may suppress the HCC progression by certain signal pathways. However, the underlying signal pathway remains largely unknown. The interactions between circMTO1 and miR-541-5p were predicted through bioinformatics analysis and verified using pull-down and dual-luciferase reporter assays. CCK-8, transwell, and apoptosis assays were performed to determine the effect of miR-541-5p on HCC progression. Using bioinformatic analysis, dual-luciferase reporter assay, RT-qPCR, and western blot, ZIC1 was found to be the downstream target gene of miR-541-5p. The regulatory mechanisms of circMTO1, miR-541-5p, and ZIC1 were investigated using in vitro and in vivo rescue experiments. The results depicted that silencing circMTO1 or upregulating miR-541-5p expression facilitated HCC cell proliferation, migration, and invasion and inhibited apoptosis. CircMTO1 silencing upregulated the expression of downstream ZIC1 regulators of the Wnt/β-catenin pathway markers, β-catenin, cyclin D1, c-myc, and the mesenchymal markers N-cadherin, Vimentin, and MMP2, while the epithelial marker E-cadherin was downregulated. MiR-541-5p knockdown had the opposite effect and reversed the effect of circMTO1 silencing on the regulation of downstream ZIC1 regulators. Intratumoral injection of miR-541-5p inhibitor suppressed tumor growth and reversed the effect of circMTO1 silencing on the promotion of tumor growth in HCC. These findings indicated that circMTO1 suppressed HCC progression via the circMTO1/ miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling and epithelial-to-mesenchymal transition, making it a novel therapeutic target.

Circular RNA Circ-0006302 Promotes the Growth, Migration, and Invasion of Cholangiocarcinoma Cells by Regulating the Mir-1299/PD-L1 Axis as a Competing Endogenous RNA

2021 ◽  
Author(s):  
Weiqian Chen ◽  
Liyun Zheng ◽  
Songquan Wu ◽  
Chenying Lu ◽  
Bufu Tang ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
The Difference ◽  
Gain Loss

Abstract Background: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis, with no effective therapy other than surgical resection. Circular RNAs (circRNAs) serve as a brand-new class of transcription products among abundant cancer processes. Nevertheless, the mechanisms account for their modification in CCA remain unknown. Methods: First, microarray sequencing was applied to detect the difference of circRNAs expression between CCA and corresponding non-tumor tissues. We utilized qRT-PCR to measure circ-0006302 levels in CCA cells and specimens. Gain/loss of-function assays and animal model of CCA were performed for the purpose of revealing the functions of circ-0006302 on the invasion, migration, and proliferation of CCA. We performed dual luciferase reporter, RNA-FISH and rescue assays for clarifying the mechanism behind. Results: In CCA tissues and cell lines circ-0006302 was highly expressed relatively. In vitro, overexpression of circ-0006302 intensifies the epithelial-to-mesenchymal transition (EMT) and the invasion, migration, and growth of CCA cells; and intensifies the growth as well as metastasis of tumors in a CCA mouse model. Furthermore, it was elucidated that circ-0006302 sponged miR-1299 to upregulate PD‐L1 expression. Through the process above, circ-0006302 binds to miR-1299 and emancipates PD-L1, facilitating the invasion, migration, and proliferation in CCA cells. Momentously, the results obtained revealed that circ-0006302 silencing elevated the expression of interferon (IFN)‐γ, and interleukin (IL)‐4 but diminished the IL-10 expression, while these effects could be reversed by miR-1299 inhibitor.Conclusion: circ-0006302 silence blocked the CCA progression via intensifying miR‐1299‐targeted downregulation of PD‐L1. Our conclusion provides novel therapeutic tactics for treating this fatal disease.

scholarly journals Metformin exerts anti-cancerogenic effects and reverses epithelial-to-mesenchymal transition trait in primary human intrahepatic cholangiocarcinoma cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sabina Di Matteo ◽  
Lorenzo Nevi ◽  
Diletta Overi ◽  
Nadine Landolina ◽  
Jessica Faccioli ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Primary Cultures ◽  
Chronic Administration ◽  
Migration And Invasion ◽  
Cytokeratin 19 ◽  
Mesenchymal Transition ◽  
Therapeutic Implications

AbstractIntrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with marked resistance to chemotherapeutics without therapies. The tumour microenvironment of iCCA is enriched of Cancer-Stem-Cells expressing Epithelial-to-Mesenchymal Transition (EMT) traits, being these features associated with aggressiveness and drug resistance. Treatment with the anti-diabetic drug Metformin, has been recently associated with reduced incidence of iCCA. We aimed to evaluate the anti-cancerogenic effects of Metformin in vitro and in vivo on primary cultures of human iCCA. Our results showed that Metformin inhibited cell proliferation and induced dose- and time-dependent apoptosis of iCCA. The migration and invasion of iCCA cells in an extracellular bio-matrix was also significantly reduced upon treatments. Metformin increased the AMPK and FOXO3 and induced phosphorylation of activating FOXO3 in iCCA cells. After 12 days of treatment, a marked decrease of mesenchymal and EMT genes and an increase of epithelial genes were observed. After 2 months of treatment, in order to simulate chronic administration, Cytokeratin-19 positive cells constituted the majority of cell cultures paralleled by decreased Vimentin protein expression. Subcutaneous injection of iCCA cells previously treated with Metformin, in Balb/c-nude mice failed to induce tumour development. In conclusion, Metformin reverts the mesenchymal and EMT traits in iCCA by activating AMPK-FOXO3 related pathways suggesting it might have therapeutic implications.

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