scholarly journals PSMC5 Promotes Proliferation and Metastasis of Colorectal Cancer by Activating Epithelial–Mesenchymal Transition Signaling and Modulating Immune Infiltrating Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Zirui He ◽  
Xiao Yang ◽  
Ling Huang ◽  
Leqi Zhou ◽  
Sen Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Immune Therapy ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Functional Assays ◽  
Infiltrating Cells ◽  
Proliferation And Metastasis ◽  
Public Datasets ◽  
Proliferation And Invasion

We designed the present study to access the roles and mechanisms of PSMC5 in colorectal cancer (CRC). Transcriptomic and clinical data from public datasets and our center were retrospectively analyzed. Functional assays were performed to investigate the effects of PSMC5 on CRC cells. The results showed that PSMC5 was significantly higher in cancer than normal tissues. Moreover, patients with higher expression of PSMC5 showed poorer prognosis. Silencing of PSMC5 dramatically suppressed the proliferation and invasion of CRC cells, while overexpression led to the opposite. In addition, we screened downstream targets and found that PSMC5 regulates multiple pathways including epithelial–mesenchymal transition, hypoxia, and immune response. Consistently, we found that PSMC5 was negatively correlated with levels of CD8 + T cells and B cells while promoting infiltration of macrophages and neutrophils. Collectively, these findings suggested that PSMC5 was a promising biomarker and target for immune therapy for CRC.

scholarly journals MiR-1-3p Suppresses Colorectal Cancer Cell Proliferation and Metastasis by Inhibiting YWHAZ-Mediated Epithelial–Mesenchymal Transition

2021 ◽  
Vol 11 ◽  
Author(s):  
Guanghong Du ◽  
Xuelian Yu ◽  
Yun Chen ◽  
Wangting Cai
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Colorectal Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis ◽  
Proliferation And Invasion ◽  
Cell Proliferation And Metastasis

BackgroundColorectal cancer (CRC) is regarded as one of the most common malignancies in the world. MiR-1-3p was reported to be a tumor suppressor in CRC. However, the mechanisms have not been fully elucidated.MethodsTo identify CRC-associated miRNA, microarray data set GSE30454 was downloaded from the Gene Expression Omnibus database (GEO), and miR-1-3p was screened out as a candidate. The expression of miR-1-3p was detected using quantitative real-time polymerase chain reaction (qRT-PCR) in CRC cell lines and tissues. CCK-8 assay and transwell invasion assay were performed to determine CRC cell line proliferation and invasion, respectively. The levels of YWHAZ and EMT-associated proteins were detected using western blotting.ResultsBioinformatic analysis showed that miR-1-3p was downregulated in CRC tissues, which is verified by our experimental validation. The overexpression of miR-1-3p significantly suppressed CRC cell proliferation and invasion. Further studies showed that YWHAZ was a direct target of miR-1-3p and mediated epithelial–mesenchymal transition (EMT) modulated by miR-1-3p.ConclusionOur results demonstrated that miR-1-3p suppresses colorectal cancer cell proliferation and metastasis through regulating YWHAZ-mediated EMT, which may support a novel therapeutic strategy for CRC patients.

scholarly journals miR551b Regulates Colorectal Cancer Progression by Targeting the ZEB1 Signaling Axis

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 735 ◽  
Author(s):  
Kwang Seock Kim ◽  
Dongjun Jeong ◽  
Ita Novita Sari ◽  
Yoseph Toni Wijaya ◽  
Nayoung Jun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Xenograft Model ◽  
Mesenchymal Transition ◽  
Normal Tissues

Our current understanding of the role of microRNA 551b (miR551b) in the progression of colorectal cancer (CRC) remains limited. Here, studies using both ectopic expression of miR551b and miR551b mimics revealed that miR551b exerts a tumor suppressive effect in CRC cells. Specifically, miR551b was significantly downregulated in both patient-derived CRC tissues and CRC cell lines compared to normal tissues and non-cancer cell lines. Also, miR551b significantly inhibited the motility of CRC cells in vitro, including migration, invasion, and wound healing rates, but did not affect cell proliferation. Mechanistically, miR551b targets and inhibits the expression of ZEB1 (Zinc finger E-box-binding homeobox 1), resulting in the dysregulation of EMT (epithelial-mesenchymal transition) signatures. More importantly, miR551b overexpression was found to reduce the tumor size in a xenograft model of CRC cells in vivo. Furthermore, bioinformatic analyses showed that miR551b expression levels were markedly downregulated in the advanced-stage CRC tissues compared to normal tissues, and ZEB1 was associated with the disease progression in CRC patients. Our findings indicated that miR551b could serve as a potential diagnostic biomarker and could be utilized to improve the therapeutic outcomes of CRC patients.

scholarly journals Inhibited Long Non-Coding RNA OIP5-AS1 Elevated microRNA-92a to Suppress Proliferation and Metastasis of Ovarian Cancer Cells by Silencing ITGA6

2020 ◽  
Author(s):  
Yujue Wang ◽  
Lingling Li ◽  
Xun Zhang ◽  
Xiaolan Zhao
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Interacting Protein ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Gene Assay ◽  
Proliferation And Metastasis ◽  
Integrin Alpha 6

Abstract Objective: Over the years, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as essential biomarkers during the development of malignancies. This study was performed to verify the roles of lncRNA opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) and miR-92a in ovarian cancer (OC).Methods: OIP5-AS1, miR-92a and ITGA6 expression in tissues and cells was assessed. The screened OC cells were respectively with integrin alpha 6 (ITGA6)/OIP5-AS1 silenced vector, miR-92a mimic/inhibitor or their negative controls. The viability, migration, invasion and apoptosis of the cells were determined and the levels of epithelial-mesenchymal transition (EMT)-related proteins were also measured. The interactions between OIP5-AS1 and miR-92a, and between miR-92a and ITGA6 were confirmed by dual luciferase report gene assay and/or RNA pull-down assay.Results: OIP5-AS1 and ITGA6 were upregulated while miR-92a was downregulated in OC tissues versus the adjacent normal tissues. Inhibited OIP5-AS1 or elevated miR-92a repressed EMT, viability, migration and invasion of OC cells, and promoted OC cell apoptosis. These effects that induced by silenced OIP5-AS1 could be reversed by miR-92a inhibitor. The reduction of ITGA6 restricted EMT in OC cells. MiR-92a was a target of OIP5-AS1 and ITGA6 was targeted by miR-92a.Conclusion: OIP5-AS1 silencing promoted miR-92a to repress proliferation and metastasis of OC cells through inhibiting ITGA6. This research may provide potential biomarkers for OC.

scholarly journals The DDX39B/FUT3/TGFβR-I axis promotes tumor metastasis and EMT in colorectal cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chengcheng He ◽  
Aimin Li ◽  
Qiuhua Lai ◽  
Jian Ding ◽  
Qun Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Splicing ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Cytoplasmic Rna

AbstractDDX39B is a member of the DEAD box (DDX) RNA helicase family required for nearly all cellular RNA metabolic processes. The exact role and potential molecular mechanism of DDX39B in the progression of human colorectal cancer (CRC) remain to be investigated. In the present study, we demonstrate that DDX39B expression is higher in CRC tissues than in adjacent normal tissues. Gain- and loss-of-function assays revealed that DDX39B facilitates CRC metastasis in vivo and in vitro. Mechanistically, RNA-sequencing (RNA-seq) and RNA-binding protein immunoprecipitation-sequencing (RIP-seq) showed that DDX39B binds directly to the FUT3 pre-mRNA and upregulates FUT3 expression. Splicing experiments in vitro using a Minigene assay confirmed that DDX39B promotes FUT3 pre-mRNA splicing. A nuclear and cytoplasmic RNA separation assay indicates that DDX39B enhances the mRNA export of FUT3. Upregulation of FUT3 accelerates the fucosylation of TGFβR-I, which activates the TGFβ signaling pathway and eventually drives the epithelial–mesenchymal transition (EMT) program and contributes to CRC progression. These findings not only provide new insight into the role of DDX39B in mRNA splicing and export as well as in tumorigenesis, but also shed light on the effects of aberrant fucosylation on CRC progression.

scholarly journals miRNA-6715-5p Inhibits Cellular Proliferation and Invasion in Colorectal Cancer by Directly Targeting CST4

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Ding Shi ◽  
Zheng Zhou ◽  
Shun Zhang
Keyword(s):  
Colorectal Cancer ◽  
Cellular Proliferation ◽  
Quantitative Polymerase Chain Reaction ◽  
Normal Tissues ◽  
Reporter Assays ◽  
Proliferation And Metastasis ◽  
Cancer Tissues ◽  
The Relationship ◽  
Proliferation And Invasion ◽  
Hct116 Cells

Background. Data on the correlation between CST4 and colorectal cancer (CRC) metastasis are scarce. The aim of this study was to analyze CST4 expression and investigate its biological roles and related microRNA- (miRNA-) mediated regulation in CRC. Methods. The expression of CST4 was examined in cancer tissues and their corresponding adjacent normal tissues from 40 gastric adenocarcinoma patients. The expression level of CST4 in specimens (cancer and normal tissues) was assessed through immunohistochemistry and/or quantitative polymerase chain reaction. miRNAs targeting CST4 in CRC were predicted by bioinformatics software. CST4 was knocked down in HCT116 cells and candidate miRNAs were transfected into HCT116 cells, and the effects of CST4 knockdown and miRNA transfection on cell proliferation and invasion were examined using CCK8, cell colony formation, and Transwell migration assays. Luciferase double-reporter assays were performed to verify the relationship between miRNA and CST4. Results. The expression of CST4 in CRC tissues was significantly higher than that in normal paracancerous tissues, but the results for miRNA-6715-5p were opposite. Regardless of CST4 knockdown or miRNA-6715-5p overexpression, the proliferation and invasion ability of HCT116 cells decreased significantly. Luciferase double-reporter assays showed that the upregulation of miR-6715-5p significantly reduced the luciferase activities of the CST4 3′-UTR plasmid in HCT116 cells. Conclusion. CST4 may be involved in CRC proliferation and metastasis. miRNA-6715-5p directly targets CST4 and negatively regulates its expression.

scholarly journals miR-185 Inhibits the Proliferation and Invasion of Non-Small Cell Lung Cancer by Targeting KLF7

2019 ◽  
Vol 27 (9) ◽  
pp. 1015-1023 ◽  
Author(s):  
Lili Zhao ◽  
Yao Zhang ◽  
Jiaoxia Liu ◽  
Wei Yin ◽  
Dan Jin ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Cancer Types ◽  
Proliferation And Invasion

MicroRNAs (miRNAs) are short endogenous noncoding RNAs that frequently play vital roles in many cancer types. Herein we demonstrated that miR-185 was remarkably downregulated in NSCLC tissues compared with adjacent normal tissues. A lower level of miR-185 was associated with lymph node metastasis. Functional assays showed that upregulation of miR-185 inhibited the proliferation, colony formation, and invasion capacities of NSCLC cells in vitro. Furthermore, we found that miR-185 suppressed the epithelial‐mesenchymal transition (EMT) process. Bioinformatics analysis and luciferase reporter gene assays revealed that Kruppel-like factor 7 (KLF7) was the target of miR-185. Overexpression of miR-185 reduced the expression of KLF7 in NSCLC cells. Upregulation of KLF7 partly neutralized the inhibitory effects of miR-185 on the proliferation and invasion of NSCLC. Additionally, we confirmed that miR-185 suppressed the tumor growth of NSCLC A549 cells in vivo. Taken together, these results demonstrate that miR-185 acts as a suppressor by targeting KLF7 in NSCLC.

Exposure to desflurane anesthesia confers colorectal cancer cells metastatic capacity through deregulation of miR-34a/LOXL3 

2020 ◽  
Author(s):  
Junyi Ren ◽  
Xiaopeng Wang ◽  
Gang Wei ◽  
Yajing Meng
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Protective Role ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Elevated Expression ◽  
Public Datasets

Abstract Background: Due to high potency and low toxicity, desflurane has been wildly used during surgery. Recent evidence that the use of desflurane was associated with colorectal cancer (CRC) tumor metastasis and poor prognosis raising concerns about the safety of desflurane. However, the mechanism was uncovered.Methods: CRC cells were exposed to desflurane, the changes in morphology and epithelial-mesenchymal transition (EMT)-related genes were evaluated. Transwell assay was used to study the migration and invasion effect. Xenograft was performed to study the tumor formation ability of desflurane-treated cells in vivo. Dual luciferase reporter assay was conducted to verify the target of miR-34a. Knockdown or overexpression of LOXL3 was used to investigate the mechanism of desflurane-induced EMT. The association of LOXL3 with CRC molecular subtypes and clinical relevance was studied by analysis of public datasets. Results: Exposure to desflurane induced EMT, migration, and invasion in CRC cells. Mice injected with desflurane-treated cells formed more tumors in the lungs. Downregulation of miR-34a and upregulation of LOXL3 were required for desflurane-induced EMT in CRC cells. LOXL3 was a direct target of miR-34a. Overexpression of LOXL3 rescued miR-34a-repressed EMT after exposure to desflurane. Elevated expression of LOXL3 was enriched in CMS4 and CRIS-B subtypes. Patients with high expression of LOXL3 showed more lymph node metastasis, as well as poor survival.Conclusion: Desflurane induced EMT and metastasis in CRC through deregulation of miR-34a/LOXL3 axis. Clinical miR-34a mimic or inhibitor targeting LOXL3 might have a potential protective role when CRC patients anesthetized by desflurane.

scholarly journals MicroRNA-520b Functions as a Tumor Suppressor in Colorectal Cancer by Inhibiting Defective in Cullin Neddylation 1 Domain Containing 1 (DCUN1D1)

2018 ◽  
Vol 26 (4) ◽  
pp. 593-604 ◽  
Author(s):  
Jing Xiao ◽  
Guang Li ◽  
Jingyu Zhou ◽  
Shalong Wang ◽  
Dongcai Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Epithelial Mesenchymal Transition ◽  
Epithelial Cell Line ◽  
Intestinal Epithelial ◽  
Mesenchymal Transition ◽  
Small Noncoding Rnas ◽  
Normal Tissues ◽  
Novel Target

MicroRNAs (miRs), a class of small noncoding RNAs, are important regulators for gene expression through directly binding to the 3′-untranslated region (3′-UTR) of their target mRNA. Recently, downregulation of miR-520b has been observed in several common human cancers. However, the exact role of miR-520b in colorectal cancer (CRC) has not previously been studied. In this study, our data showed that miR-520b was significantly downregulated in CRC and cell lines when compared with adjacent normal tissues and a normal intestinal epithelial cell line. Low expression of miR-520b was notably associated with the malignant progress and a shorter survival time for CRC patients. Restoration of miR-520b inhibited cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) in CRC cells. Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was then identified as a novel target gene of miR-520b in CRC cells. The expression of DCUN1D1 was significantly increased in CRC, with a negative correlation to miR-520b expression in CRC tissues. Moreover, a high expression of DCUN1D1 was significantly associated with the malignant progress and a poor prognosis for CRC patients. Furthermore, overexpression of DCUN1D1 rescued the miR-520b-mediated malignant phenotypes and EMT in CRC cells. The data demonstrate that miR-520b functions as a tumor suppressor in CRC through targeting DCUN1D1, suggesting that miR-520b may become a potential therapeutic target for the treatment of CRC.

scholarly journals Effect of ISM1 on the Immune Microenvironment and Epithelial-Mesenchymal Transition in Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuhui Wu ◽  
Xiaojing Liang ◽  
Junjie Ni ◽  
Rongjie Zhao ◽  
Shengpeng Shao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathways ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Normal Tissues

Background: An increasing number of studies have shown that Isthmin 1 (ISM1), a secreted protein, is important in tumorigenesis and invasion, including in colorectal cancer (CRC). However, the mechanisms are still unclear. This study aims to explore the function and prognosis capacity of ISM1 in CRC.Methods: We investigated the expression of ISM1 in 18 CRC tissues vs. adjacent normal tissues from GSE50760, 473 CRC tissues vs. 41 normal tissues from The Cancer Genome Atlas (TCGA), and across gastrointestinal cancer types. Differences were further confirmed in CRC tissues via quantitative real-time polymerase chain reaction (qRT-PCR). Then, we analyzed correlations between clinicopathologic features and ISM1 expression, including prognostic prediction value, using the Kaplan–Meier method and multivariate Cox regression. Gene set enrichment analysis (GSEA) was performed to identify ISM1-related pathways. In vitro experiments were performed to verify the role of ISM1 in epithelial-mesenchymal transition (EMT) and CRC progression.Results: Multiple datasets showed that ISM1 is upregulated in CRC tissues, which was validated. Patients with higher ISM1 expression had shorter overall survival (OS), and ISM1 expression served as an independent prognostic factor. Enrichment analysis showed that ISM1 upregulation was positively correlated with cancer-related pathways, such as EMT, hypoxia, and the Notch and KRAS signaling pathways. We were exclusively interested in the connection between ISM1 and EMT because 71% of genes in this pathway were significantly positively co-expressed with ISM1, which may account for why patients with higher ISM1 expression are prone to regional lymph node involvement and progression to advanced stages. In addition, we found that ISM1 was positively correlated with multiple immunosuppressive pathways such as IL2/STAT5, TNF-α/NF-κB, and TGF-β, and immune checkpoints, including PD-L1, PD-1, CTLA-4, and LAG3, which may account for upregulation of ISM1 in immunotherapy-resistant patients. Notably, through in vitro experiments, we found that ISM1 promoted EMT and colon cancer cell migration and proliferation.Conclusion: ISM1 is critical for CRC development and progression, which enhances our understanding of the low response rate of CRC to immunotherapy via immunosuppressive signaling pathways.

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