scholarly journals Exosome-Transmitted miR-128 Targets CCL18 to Inhibit the Proliferation and Metastasis of Urothelial Carcinoma

2022 ◽  
Vol 8 ◽  
Author(s):  
Donghao Shang ◽  
Yuting Liu ◽  
Zhenghao Chen
Keyword(s):  
Nude Mice ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
T24 Cells ◽  
Friendship Hospital ◽  
And Migration

Objective: To investigate the regulatory function of exosome-transmitted miR-128 and chemokine (C-C motif) ligand 18 (CCL18) on urothelial carcinomas (UCs).Methods: Tumor tissues, paracancerous tissues, and serum were collected from 20 patients with UCs (diagnosed at Beijing Friendship Hospital, Capital Medical University). CCL18 was detected by immunohistochemistry and ELISA. PCR was used to measure the expression levels of CCL18 and mir-183, miR-128, mir-33a in UCs. We acquired exosomes from mesenchymal stem cells and synthesized exosomes overexpressing miR-128 (HMSC-128-EV). The effects of miR-128 on the migration and invasion abilities, apoptosis and epithelial-mesenchymal transition of BUC T24 cells were investigated by co-culturing HMSC-128-EV. The therapeutic potential of miR-128 on disease models was explored by injecting HMSC-128-EV into nude mice.Results: The expression of CCL18 in UCs was significantly higher than that in normal tissues (p < 0.05), and the serum level of CCL18 in patients with UC was significantly increased compared with those in healthy controls (p < 0.05). CCL18 overexpression or downregulation enhanced or suppressed the proliferation, migration and invasion of BUC T24 cells, resectively (p < 0.05). The exosome-transmitted miR-128 can inhibit cell proliferation (p < 0.05), invasion (p < 0.05), and migration (p < 0.05) in UCs, and these effects can be reversed by CCL18. In terms of apoptosis, miR-128 was able to promote the occurrence of BUC T24 apoptosis (p < 0.05), which can also be reversed by CCL18. In addition, miR-128 can inhibit the proliferation (p < 0.05) and metastasis (p < 0.05) of UCs in nude mice.Conclusion: The miR-128 inhibits the proliferation, invasion, migration of UCs, and promotes its apoptosis by regulating CCL18 secretion.

scholarly journals HOXC10 promotes growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway

2021 ◽  
Author(s):  
Yuanxin Miao ◽  
Weina Zhang ◽  
Su Liu ◽  
Xiangfeng Leng ◽  
Chunnan Hu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Melanoma Cells ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Slug Expression ◽  
Melanoma Patients ◽  
And Migration

Abstract Homeobox C10 (HOXC10) has been reported to participate in various cancers. However, the involvement of HOXC10 in melanoma is still remains unknown. Here, we attempted to determine whether HOXC10 can affect the development of melanoma. We separated melanoma tissues and the matched tumor-adjacent normal tissues from melanoma patients, and examined HOXC10 expression in the melanoma cells and tissues. Comparing with the tumor-adjacent normal tissues, HOXC10 was up-regulated in melanoma tissues. Melanoma cells also displayed an up-regulation of HOXC10. Moreover, HOXC10 overexpression promoted cell proliferation, clone formation and inhibited apoptosis of melanoma cells. HOXC10 up-regulation also enhanced migration, invasion and epithelial-mesenchymal transition (EMT) in melanoma cells. Additionally, HOXC10 accelerated Slug expression by interacting with Slug, and activating the promoter of Slug. Slug activated the YAP/TAZ signaling pathway, which was reversed by HOXC10 silencing. The in vitro assays demonstrated that inhibition of HOXC10 significantly repressed tumor growth and lung metastasis of melanoma in mice by inhibiting Slug and YAP/TAZ signaling pathway. In conclusion, this work demonstrated that HOXC10 promoted growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway. Therefore, this study suggests that inhibition of HOXC10 has therapeutic potential in melanoma.

scholarly journals HOXC10 promotes growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuanxin Miao ◽  
Weina Zhang ◽  
Su Liu ◽  
Xiangfeng Leng ◽  
Chunnan Hu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Melanoma Cells ◽  
In Vitro Assays ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Slug Expression ◽  
And Migration

AbstractHomeobox C10 (HOXC10) has been reported to participate in various cancers. However, the involvement of HOXC10 in melanoma is still unknown. Here, we attempted to determine whether HOXC10 can affect the development of melanoma. We separated melanoma tissues and the matched tumor-adjacent normal tissues from melanoma patients, and examined HOXC10 expression in the melanoma cells and tissues. Comparing with the tumor-adjacent normal tissues, HOXC10 was up-regulated in melanoma tissues. Melanoma cells also displayed an up-regulation of HOXC10. Moreover, HOXC10 inhibition suppressed cell proliferation, clone formation and promoted apoptosis of melanoma cells. Knockdown of HOXC10 also retarded migration, invasion and epithelial–mesenchymal transition (EMT) in melanoma cells. Additionally, HOXC10 accelerated Slug expression by interacting with Slug, and activating the promoter of Slug. Slug activated the YAP/TAZ signaling pathway, which was reversed by HOXC10 silencing. The in vitro assays demonstrated that inhibition of HOXC10 significantly repressed tumor growth and lung metastasis of melanoma in mice by inhibiting Slug and YAP/TAZ signaling pathway. In conclusion, this work demonstrated that HOXC10 promoted growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway. Therefore, this study suggests that inhibition of HOXC10 has therapeutic potential in melanoma.

scholarly journals Lipocalin 2 induces the epithelial–mesenchymal transition in stressed endometrial epithelial cells: possible correlation with endometriosis development in a mouse model

Reproduction ◽  
2014 ◽  
Vol 147 (2) ◽  
pp. 179-187 ◽  
Author(s):  
Chi-Jr Liao ◽  
Pei-Tzu Li ◽  
Ying-Chu Lee ◽  
Sheng-Hsiang Li ◽  
Sin Tak Chu
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Lipocalin 2 ◽  
Mesenchymal Transition ◽  
Endometrial Cells ◽  
Cellular Microenvironments ◽  
And Migration ◽  
Endometrial Epithelial Cells

Lipocalin 2 (LCN2) is an induced stressor that promotes the epithelial–mesenchymal transition (EMT). We previously demonstrated that the development of endometriosis in mice correlates with the secretion of LCN2 in the uterus. Here, we sought to clarify the relationship between LCN2 and EMT in endometrial epithelial cells and to determine whether LCN2 plays a role in endometriosis. Antibodies that functionally inhibit LCN2 slowed the growth of ectopic endometrial tissue in a mouse model of endometriosis, suggesting that LCN2 promotes the formation of endometriotic lesions. Using nutrient deprivation as a stressor, LCN2 expression was induced in cultured primary endometrial epithelial cells. As LCN2 levels increased, the cells transitioned from a round to a spindle-like morphology and dispersed. Immunochemical analyses revealed decreased levels of cytokeratin and increased levels of fibronectin in these endometrial cells, adhesive changes that correlate with induction of cell migration and invasion.Lcn2knockdown also indicated that LCN2 promotes EMT and migration of endometrial epithelial cells. Our results suggest that stressful cellular microenvironments cause uterine tissues to secrete LCN2 and that this results in EMT of endometrial epithelial cells, which may correlate with the development of ectopic endometriosis. These findings shed light on the role of LCN2 in the pathology of endometrial disorders.

scholarly journals RON Mediates Tumor-Promoting Effects in Endometrial Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Qin Yu ◽  
Jianzhang Wang ◽  
Tiantian Li ◽  
Xinxin Xu ◽  
Xinyue Guo ◽  
...  
Keyword(s):  
Nude Mice ◽  
Reproductive Tract ◽  
Epithelial Mesenchymal Transition ◽  
Endometrial Adenocarcinoma ◽  
Female Reproductive Tract ◽  
Migration And Invasion ◽  
Smad Pathway ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells

Endometrial adenocarcinoma is one of the most prevalent female reproductive tract cancers in the world, and the development of effective treatment is still the main goal of its current research. Epithelial-mesenchymal transition (EMT) plays a significant part in the occurrence and development of epithelial carcinoma, including endometrial adenocarcinoma. Recepteur d’origine nantais (RON) induces EMT and promotes proliferation, migration, and invasion in various epithelial-derived cancers, but its role in endometrial adenocarcinoma is still poorly studied. The purpose of this study is to verify the overexpression of RON in endometrial adenocarcinoma and to explore its specific roles. RON expression in tumor lesions was verified by immunohistochemical staining, HEC-1B cells were used to construct stable cell lines with RON overexpression or knockdown to investigate the effects of RON on the function of endometrial adenocarcinoma cells, and xenotransplantation experiment was carried out in nude mice to explore the effect of RON on the growth of endometrial adenocarcinoma in vivo. This study revealed that RON could promote the proliferation, migration, and invasion of HEC-1B cells and induce EMT, and these effects were regulated through the Smad pathway. RON overexpression could promote growth of endometrial adenocarcinoma cells in nude mice, while its inhibitor BMS777607 could restrict this role. RON played an important role in endometrial adenocarcinoma and had a potential to become a new therapeutic target for endometrial adenocarcinoma.

scholarly journals Disruption of Cancer Metabolic SREBP1/miR-142-5p Suppresses Epithelial–Mesenchymal Transition and Stemness in Esophageal Carcinoma

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 7 ◽  
Author(s):  
Chih-Ming Huang ◽  
Chin-Sheng Huang ◽  
Tung-Nien Hsu ◽  
Mao-Suan Huang ◽  
Iat-Hang Fong ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Survival Rate ◽  
Tumor Suppressor ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Regulatory Element ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
E Cadherin

Elevated activity of sterol regulatory element-binding protein 1 (SREBP1) has been implicated in the tumorigenesis of different cancer types. However, the functional roles of SREBP1 in esophageal cancer are not well appreciated. Here, we aimed to investigate the therapeutic potential of SREBP1 and associated signaling in esophageal cancer. Our initial bioinformatics analyses showed that SREBP1 expression was overexpressed in esophageal tumors and correlated with a significantly lower overall survival rate in patients. Additionally, tumor suppressor miR-142-5p was predicted to target SREBP1/ZEB1 and a lower miR-142-5p was correlated with poor prognosis. We then performed in vitro experiments and showed that overexpressing SREBP1 in OE33 cell line led to increased abilities of colony formation, migration, and invasion; the opposite was observed in SREBP1-silenced OE21cells and SREBP1-silencing was accompanied by the reduced mesenchymal markers, including vimentin (Vim) and ZEB1, while E-cadherin and tumor suppressor miR-142-5p were increased. Subsequently, we first demonstrated that both SREBP1 and ZEB1 were potential targets of miR-142-5p, followed by the examination of the regulatory circuit of miR-142-5p and SREBP1/ZEB1. We observed that increased miR-142-5p level led to the reduced tumorigenic properties, such as migration and tumor sphere formation, and both observations were accompanied by the reduction of ZEB1 and SREBP1, and increase of E-cadherin. We then explored the potential therapeutic agent targeting SREBP1-associated signaling by testing fatostatin (4-hydroxytamoxifen, an active metabolite of tamoxifen). We found that fatostatin suppressed the cell viability of OE21 and OE33 cells and tumor spheres. Interestingly, fatostatin treatment reduced CD133+ population in both OE21 and OE33 cells in concert of increased miR-142-5p level. Finally, we evaluated the efficacy of fatostatin using a xenograft mouse model. Mice treated with fatostatin showed a significantly lower tumor burden and better survival rate as compared to their control counterparts. The treatment of fatostatin resulted in the reduced staining of SREBP1, ZEB1, and Vim, while E-cadherin and miR-142-5p were increased. In summary, we showed that increased SREBP1 and reduced miR-142-5p were associated with increased tumorigenic properties of esophageal cancer cells and poor prognosis. Preclinical tests showed that suppression of SREBP1 using fatostatin led to the reduced malignant phenotype of esophageal cancer via the reduction of EMT markers and increased tumor suppressor, miR-142-5p. Further investigation is warranted for the clinical use of fatostatin for the treatment of esophageal malignancy.

scholarly journals CHIP-mediated CIB1 ubiquitination regulated epithelial–mesenchymal transition and tumor metastasis in lung adenocarcinoma

2020 ◽  
Author(s):  
Yuanqi Liu ◽  
Yanwu Zhou ◽  
Pengfei Zhang ◽  
Xizhe Li ◽  
Chaojun Duan ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Clinicopathological Characteristics ◽  
Interacting Protein ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Ubiquitin E3 Ligase ◽  
And Migration

Abstract CIB1 is a homolog of calmodulin that regulates cell adhesion, migration, and differentiation. It has been considered as an oncogene in many tumor cells; however, its role in lung adenocarcinoma (LAC) has not been studied. In this study, the expression levels of CIB1 in LAC tissues and adjacent normal tissues were examined by immunohistochemistry, and the relationship between CIB1 expression and patient clinicopathological characteristics was analyzed. The effects of CIB1 on epithelial–mesenchymal transition (EMT), migration, and metastasis of LAC cells were determined in vitro and vivo. Proteins interacting with CIB1 were identified using electrospray mass spectrometry (LS-MS), and CHIP was selected in the following assays. Carboxyl-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin E3 ligase. We show that CHIP can degrade CIB1 via promoting polyubiquitination of CIB1 and its subsequent proteasomal degradation. Besides, lysine residue 10 and 65 of CIB1 is the ubiquitinated site of CIB1. Furthermore, CHIP-mediated CIB1 downregulation is critical for the suppression of metastasis and migration of LAC. These results indicated that CHIP-mediated CIB1 ubiquitination could regulate epithelial–mesenchymal and tumor metastasis in LAC.

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.

MiR-21 Promotes the Invasion and Metastasis of Gastric Cancer Cells by Activating Epithelial-Mesenchymal Transition

2019 ◽  
Vol 60 (5-6) ◽  
pp. 208-218 ◽  
Author(s):  
Tao Xiao ◽  
Zhigang Jie
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Invasion And Metastasis ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Background: Gastric cancer (GC) is one of the most common malignant tumors. It is likely to occur in lymph nodes and is prone to distant metastasis in its early stages, which portends a poor prognosis. Previous studies have shown that miRNA-21 was abnormally highly expressed and associated with early metastasis in GC, but the mechanism by which it regulates the invasion and metastasis of GC has not been elucidated. Methods: Epithelial-mesenchymal transition (EMT) is an important pathologic basis of tumor invasion and metastasis, and in this study, the relationship between miRNA-21 and EMT in GC invasion and metastasis was investigated using RT-qPCR, Western blot, and wound scratch and transwell assays. Results: We found that miRNA-21 expression in GC cell lines was higher than in a gastric mucosal epithelial cell line. After transfection with an miRNA-21 mimic, the upregulation of EMT was found to promote migration and invasion of MGC-803 cells. However, the downregulation of EMT was found to accompany the inhibition of invasion and migration of GC cells after downregulation of miRNA-21 expression due to the transfection of an miRNA-21 inhibitor. Conclusions: These findings suggest that miRNA-21 might promote the invasion and metastasis of GC by upregulating EMT.

Kaempferol ameliorates the regulatory effects of PVT1/miR-214 on epithelial–mesenchymal transition through the PAK4/β-catenin axis in SRA01/04 cells

2021 ◽  
Author(s):  
Jing Huang ◽  
Zhixi Chen ◽  
Zhihao Lai ◽  
Yang Liu ◽  
Dongyi Yu ◽  
...  
Keyword(s):  
Protein Interactions ◽  
High Glucose ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Protein Determination ◽  
Mesenchymal Transition ◽  
Direct Target ◽  
Regulatory Effects ◽  
And Migration ◽  
Invasion Assays

Aim: To investigate whether kaempferol exhibits a protective effect on high glucose-induced epithelial–mesenchymal transition (EMT) by mediating the  PVT1/ miR-214 and PAK4/β-catenin pathways in SRA01/04 cells. Methods & methods: qRT-PCR and western blot assays were used for gene and protein determination, and migration and invasion assays were conducted. A coimmunoprecipitation assay was used for determining protein interactions. Results: High glucose effectively upregulated PVT1 expression, downregulated miR-214 expression and promoted cell migration and invasion. Kaempferol attenuated high glucose-induced EMT by increasing PVT1 expression and decreasing miR-214 expression. PAK4 was identified as a direct target of miR-214. PAK4 overexpression could rescue the effects of PVT1 deficiency on SRA01/04 cells. Conclusion: Kaempferol ameliorated the regulatory effects of PVT1/ miR-214 on high glucose-induced EMT through PAK4/β-catenin in SRA01/04 cells.

Latent Membrane Protein 1 Antibody Inhibits Cell Migration, Invasion and Epithelial-Mesenchymal Transition of Nasopharyngeal Carcinoma Stem Cell via Regulating Wnt/β-Catenin Signaling Pathway

2020 ◽  
Vol 10 (7) ◽  
pp. 930-938
Author(s):  
Dawei Zhang ◽  
Lin Xiong ◽  
Liang Li ◽  
Yuan Chen ◽  
Xiaojun Tang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Animal Experiments ◽  
Migration And Invasion ◽  
Western Blot Assay ◽  
Mesenchymal Transition ◽  
Potential Strategy ◽  
And Migration

Objective: In order to investigate the effects of LMP1-Fab antibody on Nasopharyngeal carcinoma (NPC) cancer stem cells (CSCs). Methods/ Results: Methods were performed to study the effects of LMP1-Fab antibody on NPC CSCs in vivo and in vitro, for example, transwell chamber assay, wound healing assay, western blot assay, quantitative real-time PCR assay animal experiments, animal fluorescence imaging, H&E staining, immunohistochemistry. We identified that LMP1 activated the migration and invasion of NPC. Whereas the LMP1-Fab antibody inhibited cell invasion, epithelial-mesenchymal transition (EMT) and migration of NPC CSCs in LMP1+ HNE2 cells. Furthermore, LMP1-Fab antibody significantly increased the expression of E-cadherin, and reduced the expressions of vimentin,N -cadherin and Slug in LMP1+ HNE2 CSCs cells. Mechanistically, LMP1-Fab antibody inhibited lung and liver metastasis by regulating the wnt/ -catenin pathway in the nude mice. Conclusion: These results suggested that the novel antibody-targeting LMP1 is likely to be a potential strategy for the treatment of NPC.

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