scholarly journals Inhibition of MIR4435-2HG on Invasion, Migration, and EMT of Gastric Carcinoma Cells by Mediating MiR-138-5p/Sox4 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Li-Fei Gao ◽  
Wei Li ◽  
Ya-Gang Liu ◽  
Cui Zhang ◽  
Wei-Na Gao ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Carcinoma Cells ◽  
The Cancer Genome Atlas ◽  
Cell Counting ◽  
Pcr Analysis ◽  
Mesenchymal Transition ◽  
Qrt Pcr

BackgroundThe previous investigations have identified that long non-coding RNA (lncRNAs) act as crucial regulators in gastric carcinoma. However, the function of lncRNA MIR4435-2HG in the modulation of gastric carcinoma remains elusive. Here, we aimed to explore the role of MIR4435-2HG in gastric carcinoma.MethodThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were applied to select the differently expressed lncRNAs in gastric carcinoma. The qRT-PCR was applied to analyze MIR4435-2HG expression in carcinoma tissues and cell lines. The effect of MIR4435-2HG on proliferation, invasion, migration, and apoptosis of gastric carcinoma cells was detected by Cell Counting Kit-8 (CCK-8) assays, transwell assays, and flow cytometry in vitro. A subcutaneous tumor model was constructed to examine the tumor growth of gastric carcinoma cells after knocking out MIR4435-2HG. RNA immunoprecipitation and luciferase reporting assays were applied to evaluate the interaction of MIR4435-2HG, miR-138-5p, and Sox4.ResultsThe bioinformatics analysis based on TCGA and GEO databases indicated that MIR4435-2HG was obviously elevated in gastric carcinoma samples. The qRT-PCR analysis revealed that MIR4435-2HG was upregulated in clinical gastric carcinoma tissues and cells. The high expression of MIR4435-2HG is associated with the poor survival rate of patients. The knockout of MIR4435-2HG could repress the proliferation, invasion, migration, and epithelial–mesenchymal transition (EMT) and accelerate the apoptosis of gastric carcinoma cells. Moreover, the deletion of MIR4435-2HG was able to attenuate the tumor growth in vivo. Mechanically, we identified that MIR4435-2HG enhanced Sox4 expression by directly interacting with miR-138-5p as a competitive endogenous RNA (ceRNA) in gastric carcinoma cells, in which Sox4 was targeted by miR-138-5p.ConclusionMIR4435-2HG is elevated in gastric carcinoma cells and contributes to the growth, metastasis, and EMT of gastric carcinoma cells by targeting miR-138-5p/Sox4 axis. MIR4435-2HG may be applied as a potential therapeutic target in gastric carcinoma.

scholarly journals Amygdalin Attenuates Airway Epithelium Apoptosis, Inflammation, and Epithelial-Mesenchymal Transition through Restraining the TLR4/NF-κB Signaling Pathway on LPS-Treated BEAS-2B Bronchial Epithelial Cells

2021 ◽  
pp. 1-11 ◽  
Author(s):  
Zhenyang Si ◽  
Biao Zhang
Keyword(s):  
Signaling Pathway ◽  
Airway Epithelium ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Cell Counting ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Tnf Α ◽  
E Cadherin

<b><i>Background:</i></b> Cough-variant asthma (CVA) is a special type of asthma, solely manifesting with coughing. Studies suggest that airway inflammation is associated with CVA pathogenesis. Amygdalin is found to have an anti-inflammatory potential, while how it affects CVA remains unexplored. <b><i>Methods:</i></b> Cytotoxicity delivered by various concentrations of LPS and amygdalin on BEAS-2B cells was determined by Cell Counting Kit-8 assay. CVA in vitro models were established via LPS exposure on BEAS-2B cells which underwent amygdalin pretreatment. Cell apoptosis was determined by flow cytometry. Production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and mucin 5AC (MUC5AC) in BEAS-2B cells was measured by ELISA and qRT-PCR. Expressions of TLR4, E-cadherin, N-cadherin, α-smooth muscle actin (SMA), vimentin, phosphorylated-p65 (p-p65), p65, phosphorylated-IκBα (p-IκBα), and IκBα in BEAS-2B cells were measured by qRT-PCR or Western blot. <b><i>Results:</i></b> LPS and high concentrations of amygdalin (over 600 μg/mL) decreased BEAS-2B cell toxicity. Exposure to LPS inhibited toxicity, enhanced apoptosis; and promoted production of TNF-α, IL-6, IL-8, and MUC5AC, increased the levels of N-Cadherin, α-SMA, vimentin, p-p65, and p-IκBα, and decreased the levels of E-cadherin and IκBα in BEAS-2B cells. Amygdalin pretreatment counteracted the effects of LPS on BEAS-2B cells. Overexpressing TLR4 reversed amygdalin-exerted effects in LPS-exposed BEAS-2B cells. <b><i>Conclusion:</i></b> Amygdalin attenuated airway epithelium apoptosis, inflammation and epithelial-mesenchymal transition through restraining the TLR4/NF-κB signaling pathway in CVA.

scholarly journals MiR-205 suppresses epithelial–mesenchymal transition and inhibits tumor growth of human glioma through down-regulation of HOXD9

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Bin Dai ◽  
Guanghua Zhou ◽  
Zhiqiang Hu ◽  
Guangtong Zhu ◽  
Beibei Mao ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Human Glioma ◽  
Mesenchymal Transition

AbstractEpithelial–mesenchymal transition (EMT) plays a pivotal role in cancer progression. Hsa-miR-205 is considered one of the fundamental regulators of EMT. In the present study, we found that miR-205 was down-regulated in glioma tissues and human glioma cells U87 and U251. Meanwhile, miR-205 overexpression enhanced E-cadherin, reduced mesenchymal markers, and decreased cell proliferation, migration, and invasion in vitro. In vivo, miR-205 suppressed tumor growth. Additionally, HOXD9 was confirmed as a direct target of miR-205. Suppression of HOXD9 by miR-205 was demonstrated by luciferase reporter assay, quantitative real time-PCR analysis, and western blot. Moreover, we observed a negative correlation between miR-205 and HOXD9 in human glioma tissues. In summary, our findings demonstrated that miR-205 suppresses glioma tumor growth, invasion, and reverses EMT through down-regulating its target HOXD9.

scholarly journals Snail Driving Alternative Splicing of CD44 by ESRP1 Enhances Invasion and Migration in Epithelial Ovarian Cancer

2017 ◽  
Vol 43 (6) ◽  
pp. 2489-2504 ◽  
Author(s):  
Le Chen ◽  
Ying Yao ◽  
Lijuan Sun ◽  
Jiajia Zhou ◽  
Minmin Miao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Alternative Splicing ◽  
Epithelial Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Regulatory Protein ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.

ASAP1 promotes tumor progression and angiogenesis and independently predicts poor prognosis and lymph node metastasis of gastric cancer

2019 ◽  
Author(s):  
Hongyu Gao ◽  
Ling Qin ◽  
Huawen Shi ◽  
Hongfeng Zhang ◽  
Chunfeng Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Node Metastasis ◽  
Tumor Cell Motility

Abstract Background: Although ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1(ASAP1) is involved in the development of various malignancies, its clinical significance and mechanism in gastric cancer (GC) remains unclear.Methods: The effects of ASAP1 on tumor progression, angiogenesis, and epithelial-mesenchymal transition were evaluated in vitro. The effects of ASAP1 on tumor growth and angiogenesis were also explored in vivo. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to gather ASAP1 expression data.Results: It showed that ASAP1 expression strongly correlated with the TNM stage (P < 0.0001) and lymph node metastasis (P < 0.0001). Multivariate analyses indicated that ASAP1 overexpression (P < 0.0001) was an independent predictor for overall survival in patients with GC. Moreover, the results revealed that ASAP1 overexpression was independently related to lymph node metastasis (P = 0.0001). ASAP1 knockdown inhibited tumor cell motility, migration, invasion, and angiogenesis, which was accompanied with the downregulation of metastatic and angiogenic biomarkers. Furthermore, ASAP1 inhibition resulted in the simultaneous downregulation of mesenchymal markers and upregulation of epithelial markers. In addition, ASAP1 promoted tumor growth and angiogenesis in the xenograft mice model. The combined datasets (TCGA and GEO) suggested that ASAP1 was associated with malignant behavior of tumor and tumor invasion, metastasis, and angiogenesis.Conclusion: To our knowledge, our study is the first to reveal that ASAP1 promotes tumor progression and angiogenesis, and indicates a prognostic potential in GCs.

scholarly journals Intestinal dysbacteriosis activates tumor-associated macrophages to promote epithelial-mesenchymal transition of colorectal cancer

2018 ◽  
Vol 24 (8) ◽  
pp. 480-489 ◽  
Author(s):  
Guangsheng Wan ◽  
Manli Xie ◽  
Hongjie Yu ◽  
Hongyu Chen
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Mice Model ◽  
Mesenchymal Transition ◽  
Tnf Α ◽  
Xenograft Mice Model ◽  
Intestinal Dysbacteriosis

In this study we investigated the association between intestinal dysbacteriosis with colorectal cancer progress and the underlying molecular mechanisms. Tumor progression was evaluated using xenograft mice model. The epithelial-mesenchymal transition (EMT) markers were quantified by both real-time PCR and immunoblotting. The serum content of IL-6 and TNF-α were measured with ELISA kits. Cell proliferation was determined by the Cell Counting Kit-8. Intestinal dysbacteriosis was successfully simulated by the administration of a large dose of antibiotics and was demonstrated to promote xenograft tumor growth and induce EMT. Accordingly, the serum concentrations of cytokines IL-6 and TNF-α were significantly increased. Furthermore, the production and secretion of IL-6 and TNF-α were remarkably elevated in macrophages isolated from intestinal dysbiotic mice in comparison with the normal counterparts, and conditioned medium from these was shown to significantly stimulate EMT process in HT29 cells in vitro. Macrophage depletion completely abrogated the pro-tumor effect of intestinal dysbacteriosis. Our results suggest that intestinal dysbacteriosis stimulates macrophage activation and subsequently induces EMT process via secreted pro-inflammatory cytokines IL-6 and TNF-α.

scholarly journals Pseudomonas aeruginosa-mannose-sensitive hemagglutinin inhibits chemical-induced skin cancer through suppressing hedgehog signaling

2020 ◽  
Vol 245 (3) ◽  
pp. 213-220
Author(s):  
Dianhui Xiu ◽  
Min Cheng ◽  
Wenlei Zhang ◽  
Xibo Ma ◽  
Lin Liu
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Skin Cancer ◽  
Hedgehog Signaling ◽  
Anticancer Agent ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Mesenchymal Transition ◽  
Anticancer Properties

Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PAM) is an inactivate P. aeruginosa with mannose-sensitive hemagglutinin. Recently, the anticancer properties of PAM against many cancers have been reported across a range of studies. However, the exact mechanism through which PAM prevents skin cancer remains unclear. The aim of this study is to show to what extent PAM could inhibit the dimethylbenzanthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin cancer. JB6 cells were treated by TPA so as to establish an in vitro model. The effects of PAM on proliferation of the cells were analyzed using cell counting kit-8 assays. Effects on epithelial–mesenchymal transition (EMT) were assayed by real-time PCR and Western blotting. A DMBA/TPA-induced skin cancer mouse model was also established. The results showed that TPA promoted EMT changes through the activation of the hedgehog (Hh) pathway, which was reversed by PAM. Moreover, PAM inhibited the cancer growth and Hh pathway in vivo. These data indicate that PAM may serve as a potential anticancer agent for the treatment of skin cancer. Impact statement Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PAM) restrained the chemical-induced skin cancer cells in vitro and in vivo partly through suppressing the Hh signaling pathway, indicating that PAM may be a promising anticancer agent for treating skin cancer.

scholarly journals A potent CBP/p300-Snail interaction inhibitor suppresses tumor growth and metastasis in wild-type p53-expressing cancer

2020 ◽  
Vol 6 (17) ◽  
pp. eaaw8500
Author(s):  
Hong-Mei Li ◽  
Yan-Ran Bi ◽  
Yang Li ◽  
Rong Fu ◽  
Wen-Cong Lv ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Effects ◽  
Creb Binding Protein ◽  
Wild Type ◽  
Mesenchymal Transition ◽  
Patients With Cancer ◽  
Wild Type P53

The zinc finger transcription factor Snail is aberrantly activated in many human cancers and associated with poor prognosis. Therefore, targeting Snail is expected to exert therapeutic benefit in patients with cancer. However, Snail has traditionally been considered “undruggable,” and no effective pharmacological inhibitors have been identified. Here, we found a small-molecule compound CYD19 that forms a high-affinity interaction with the evolutionarily conserved arginine-174 pocket of Snail protein. In aggressive cancer cells, CYD19 binds to Snail and thus disrupts Snail’s interaction with CREB-binding protein (CBP)/p300, which consequently impairs CBP/p300-mediated Snail acetylation and then promotes its degradation through the ubiquitin-proteasome pathway. Moreover, CYD19 restores Snail-dependent repression of wild-type p53, thus reducing tumor growth and survival in vitro and in vivo. In addition, CYD19 reverses Snail-mediated epithelial-mesenchymal transition (EMT) and impairs EMT-associated tumor invasion and metastasis. Our findings demonstrate that pharmacologically targeting Snail by CYD19 may exert potent therapeutic effects in patients with cancer.

scholarly journals ADAM17 promotes epithelial-mesenchymal transition via TGF-β/Smad pathway in gastric carcinoma cells

2016 ◽  
Vol 49 (6) ◽  
pp. 2520-2528 ◽  
Author(s):  
Min Xu ◽  
Hailang Zhou ◽  
Chunli Zhang ◽  
Junbo He ◽  
Hong Wei ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Carcinoma Cells ◽  
Smad Pathway ◽  
Mesenchymal Transition

scholarly journals CircSETD3 (Hsa_circ_0000567) Suppresses Hepatoblastoma Pathogenesis via Targeting the miR-423-3p/Bcl-2-Interacting Mediator of Cell Death Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Li ◽  
Haojie Wang ◽  
Zhijie Liu ◽  
Alimujiang Abudureyimu
Keyword(s):  
Regulatory Mechanism ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
Cell Counting ◽  
Dependent Manner ◽  
Mice Model ◽  
Gain Of Function ◽  
Mesenchymal Transition

Background: Up until now, the role of circSETD3 (Has_circ_0000567) in regulating cancer development has been reported in several tumors, but the role and regulatory mechanism of circSETD3 in hepatoblastoma (HB) remain unclear.Methods: The qPCR and western blotting were used to determine the mRNA and protein levels in the present study. Stability of circular RNA was detected by RNA digested experiments. The gain-of-function and rescue experiments were used to explore the function and mechanism of circSETD3 in HB. Cell counting kit-8, colony formation, transwell assay, and xenograft mice model were used to detect effects and regulatory mechanism of circSETD3/miR-423-3p/Bim axis on cell aggressive phenotype in vitro and in vivo.Results: Here, we identified that circSETD3 downregulated in both HB clinical tissues and cell lines, compared to that of normal tissues and cells. Further gain-of-function experiments validated that circSETD3 overexpression inhibited cell proliferation, viability, migration, epithelial-mesenchymal transition (EMT) and tumorigenesis, and induced cell apoptosis in HB cells. Next, we validated that miR-423-3p targeted both circSETD3 and 3′ untranslated region (3′UTR) of Bim, and circSETD3 positively regulated Bim in HB cells through sponging miR-423-3p in a competing endogenous RNA (ceRNA)-dependent manner. Furthermore, through conducting reversal experiments, we evidenced that the inhibiting effects of circSETD3 overexpression on HB development were abrogated by upregulating miR-423-3p and downregulating Bim.Conclusion: Taken together, we evidenced that circSETD3 sponged miR-423-3p to upregulate Bim, resulting in the inhibition of HB development.

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.

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