scholarly journals Deficiency of pigment epithelium-derived factor in nasopharyngeal carcinoma cells triggers the epithelial–mesenchymal transition and metastasis

2017 ◽  
Vol 8 (6) ◽  
pp. e2838-e2838 ◽  
Author(s):  
Ting Zhang ◽  
Ping Yin ◽  
Zichen Zhang ◽  
Banglao Xu ◽  
Di Che ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Pigment Epithelium ◽  
Suppressor Gene ◽  
Mesenchymal Transition ◽  
Pigment Epithelium Derived Factor ◽  
Epithelial Phenotype

AbstractDistant metastasis is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure while epithelial–mesenchymal transition (EMT) is the critical process of NPC invasion and metastasis. However, tumor-suppressor genes involved in the EMT and metastasis of NPC have not been explored clearly compared with the oncogenes. In the present study, the expression of pigment epithelium-derived factor (PEDF), a potent endogenous antitumor factor, was diminished in human NPC tissues and associated with clinicopathological and EMT features. The knockdown of PEDF induced EMT in lower metastatic NPC cell lines and overexpression of PEDF restored epithelial phenotype in higher metastatic NPC cell lines with typical EMT. The inhibition of PEDF mediated NPC cell spontaneous metastasisin vivo. LRP6/GSK3β/β-catenin signal pathway rather than AKT/GSK3βpathway was involved in the effects of PEDF on EMT. The expression of PEDF was directly downregulated by elevated miR-320c in NPC. In conclusion, our findings indicate for the first time that PEDF functions as tumor-suppressor gene in the occurrence of EMT and metastasis in NPC. PEDF could serve as a promising candidate for NPC diagnosis, prognosis and treatment.

MiR-597 Targeting 14-3-3σ Enhances Cellular Invasion and EMT in Nasopharyngeal Carcinoma Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Lisha Xie ◽  
Tao Jiang ◽  
Ailan Cheng ◽  
Ting Zhang ◽  
Pin Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Before And After

Background: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. Methods: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay. Results: miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC. Conclusion: Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.

scholarly journals MiR-130a-3p inhibits the viability, proliferation, invasion, and cell cycle, and promotes apoptosis of nasopharyngeal carcinoma cells by suppressing BACH2 expression

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Xin Chen ◽  
Bo Yue ◽  
Changming Zhang ◽  
Meihao Qi ◽  
Jianhua Qiu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Tissue Samples ◽  
Mesenchymal Transition

The aim of the present study was to explore the mechanism through which miR-130a-3p affects the viability, proliferation, migration, and invasion of nasopharyngeal carcinoma (NPC). Tissue samples were collected from the hospital department. NPC cell lines were purchased to conduct the in vitro and in vivo assays. A series of biological assays including MTT, Transwell, and wound healing assays were conducted to investigate the effects of miR-130a-3p and BACH2 on NPC cells. MiR-130a-3p was down-regulated in both NPC tissues and cell lines, whereas BACH2 was up-regulated in both tissues and cell lines. MiR-130a-3p overexpression inhibited NPC cell viability, proliferation, migration, and invasion but promoted cell apoptosis. The converse was true of BACH2, the down-regulation of which could inhibit the corresponding cell abilities and promote apoptosis of NPC cells. The target relationship between miR-130a-3p and BACH2 was confirmed. The epithelial–mesenchymal transition (EMT) pathway was also influenced by miR-130a-3p down-regulation. In conclusion, miR-130a-3p could bind to BACH2, inhibit NPC cell abilities, and promote cell apoptosis.

SOX10 induces epithelial–mesenchymal transition and contributes to nasopharyngeal carcinoma progression

2018 ◽  
Vol 96 (3) ◽  
pp. 326-331 ◽  
Author(s):  
Ping He ◽  
Xiaojie Jin
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Objective: The aim of this study was to investigate the role of SOX10 in nasopharyngeal carcinoma (NPC) and the underlying molecular mechanisms. Methods: The expression of SOX10 was initially assessed in human NPC tissues and a series of NPC cell lines through quantitative real-time PCR (qRT-PCR) and Western blot. Then, cell proliferation, cycle, migration, and the invasiveness of NPC cells with knockdown of SOX10 were examined by MTT, flow cytometry, and Transwell migration and invasion assays, respectively. Finally, nude mice tumorigenicity experiments were performed to evaluate the effects of SOX10 on NPC growth and metastasis in vivo. Results: SOX10 was significantly increased in NPC tissues and cell lines. In-vitro experiments revealed that loss of SOX10 obviously inhibited cell proliferation, migration, and invasiveness, as well as the epithelial–mesenchymal transition (EMT) process in NPC cells. In-vivo experiments further demonstrated that disrupted SOX10 expression restrained NPC growth and metastasis, especially in lung and liver. Conclusion: Taken together, our data confirmed the role of SOX10 as an oncogene in NPC progression, and revealed that SOX10 may serve as a novel biomarker for diagnosis of NPC, as well as a potential therapeutic target against this disease.

scholarly journals FEZF1-AS1 is a key regulator of cell cycle, epithelial–mesenchymal transition and Wnt/β-catenin signaling in nasopharyngeal carcinoma cells

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yunzhou Cheng
Keyword(s):  
Cell Cycle ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Expression Levels

AbstractBackground: Accumulating studies discloses that long non-coding RNAs (lncRNAs) serve important roles in human tumorigenesis, including nasopharyngeal carcinoma (NPC). The purpose of the present study was to determine the role of lncRNA FEZF1-AS1 in NPC.Materials and methods: The expression levels of FEZF1-AS1 in NPC tissues and cell lines were detected by RT-qPCR analysis. MTT assay was performed to investigate the proliferation of NPC cells in vitro, whereas the migration and invasion of NPC cells were determined by wound healing assay and transwell assay. A nude mouse tumor model was established to study the role of FEZF1-AS1 in NPC tumorigenesis in vivo. The expression levels of proteins were detected by Western blot assay.Results: The results showed that FEZF1-AS1 expression was increased in the NPC tissues and cell lines, and the higher expression of FEZF1-AS1 was closely associated with poor prognosis of NPC patients. We further observed that knockdown of FEZF1-AS1 inhibited the proliferation of NPC cells in vitro and suppressed NPC xenograft growth in vivo through inducing G2/M cell cycle arrest. The migratory and invasive abilities of NPC cells were also reduced upon FEZF1-AS1 knockdown. Moreover, we demonstrated that inhibition of FEZF1-AS1 remarkably suppressed epithelial–mesenchymal transition (EMT) and reduced β-catenin accumulation in nucleus in NPC cells.Conclusions: Collectively, we showed that FEZF1-AS1 might be a key regulator of cell cycle, EMT and Wnt/β-catenin signaling in NPC cells, which may be helpful for understanding of pathogenesis of NPC.

scholarly journals Exosomes overexpressing miR-34c inhibit malignant behavior and reverse the radioresistance of nasopharyngeal carcinoma

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Fang-Zhu Wan ◽  
Kai-Hua Chen ◽  
Yong-Chu Sun ◽  
Xi-Chan Chen ◽  
Ren-Ba Liang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Serum Samples ◽  
Mesenchymal Transition ◽  
Malignant Behavior

Abstract Background Malignant behavior and radioresistance, which severely limits the efficacy of radiation therapy (RT) in nasopharyngeal carcinoma (NPC), are associated with tumor progression and poor prognosis. Mesenchymal stem cells (MSCs) are used as a therapeutic tool in a variety of tumors. The aim of this study was to reveal the effect of tumor suppressor microRNA-34c-5p (miR-34c) on NPC development and radioresistance, as well as to confirm that exosomes derived from MSCs overexpressing miR-34c restore the sensitivity to radiotherapy in NPCs. Methods Potentially active microRNAs were screened by cell sequencing, Gene Expression Omnibus (GEO) database analysis, and analysis of clinical serum samples from 70 patients. The expression of genes and proteins was detected by Western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemistry (IHC). Proliferation, apoptosis, invasion, migration and radioresistance of NPC were detected. Luciferase reporter assays were used to verify the interactions of microRNAs with their downstream targets. MSCs exosomes were isolated by ultrafiltration and verified by electron microscopy and nanoparticle tracking technology. Results The expression of miR-34c was associated with the occurrence and radiation resistance of NPC. In vitro and in vivo experiments indicated that overexpression of miR-34c inhibit malignant behavior such as invasion, migration, proliferation and epithelial-mesenchymal transition (EMT) in NPCs by targeting β-Catenin. In addition, we found alleviated radioresistance upon miR-34c overexpression or β-catenin knockdown in NPCs. Exosomes derived from miR-34c-transfected MSCs attenuated NPC invasion, migration, proliferation and EMT. Moreover, miR-34c-overexpressing exosomes drastically increased radiation-induced apoptosis in NPC cells. Conclusion miR-34c is a tumor suppressor miR in NPC, which inhibits malignant behavior as well as radioresistance of tumor. Therefore, exogenous delivery of miR-34c to NPCs via MSC exosomes inhibits tumor progression and increases the efficiency of RT. Combination IR with miR-34c-overexpressing exosomes may be effective treatment for radioresistant NPCs.

scholarly journals YPEL3 suppresses epithelial–mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway

2016 ◽  
Vol 35 (1) ◽  
Author(s):  
Jian Zhang ◽  
Xin Wen ◽  
Xian-Yue Ren ◽  
Ying-Qin Li ◽  
Xin-Ran Tang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Western Blotting ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract Background Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored. Methods We evaluated YPEL3 expression in NPC cell lines and tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/β-catenin signaling pathway downstream genes using western blotting. Results YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial–mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin. Conclusions YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/β-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment.

scholarly journals Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Wang ◽  
Zhiwei He ◽  
Jian Xu ◽  
Peng Chen ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

AbstractAn accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.

Nano-Coated si-SNHG14 Regulated PD-L1 Expression and Decreased Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma Cells

2021 ◽  
Vol 17 (10) ◽  
pp. 1993-2002
Author(s):  
Haoran Yu ◽  
Chen Zhang ◽  
Wanpeng Li ◽  
Xicai Sun ◽  
Quan Liu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Animal Experiments ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Tumor Agent

To investigate the expression characteristics of long non-coding RNA SNHG14 in nasopharyngeal carcinoma (NPC) and its effects on epithelial-mesenchymal transition and development of nano-coated si-SNHG14 as an anti-tumor agent. The SNHG14 expression in cancerous and adjacent non-cancerous tissues was monitored using reverse transcriptionpolymerase chain reaction (RT-PCR). Gain- and loss-of-function experiments tested the regulation of SNHG14, miR- 5590-3p, and ZEB1 on PD-L1. The binding association between the above three factors was verified using bioinformatics analysis. EMT-related E-cadherin, N-cadherin, and Vimentin were tested using Western blot. Animal experiments in nude mice verified the function of SNHG14 in the EMT of NPC in vivo. The nano-coated si-SNHG14 was developed as an anti-tumor agent and was verified NPC cell in vitro. SNHG14 was upregulated in NPC tissues. Knocking down SNHG14 markedly inhibited the EMT of NPC. Additionally, the expression of ZEB1 was positively related to that of the SNHG14, while it was inversely correlated with that of miR-5590-3p. Moreover, ZEB1 transcription upregulated PD-L1 and promoted the EMT, while SNHG14 could accelerate the EMT of NPC in vivo by regulating the PD-1 and PD-L1. SNHG14-miR-5590- 3p-ZEB1 positively regulated PD-L1 and facilitate the EMT of NPC. Nano-coated si-SNHG14 significantly downregulated PD-L1 expression and decreased EMT.

scholarly journals RUNX1 suppresses breast cancer stemness and tumor growth

2018 ◽  
Author(s):  
Deli Hong ◽  
Andrew J. Fritz ◽  
Kristiaan H. Finstad ◽  
Mark P. Fitzgerald ◽  
Adam L. Viens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Tumor Suppressor ◽  
Cancer Stem Cell ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Cell Activity ◽  
Mesenchymal Transition

SummaryRecent studies have revealed that mutations in the transcription factor Runx1 are prevalent in breast tumors. Yet, how loss of Runx1 contributes to breast cancer (BCa) remains unresolved. We demonstrate for the first time that Runx1 represses the breast cancer stem cell (BCSC) phenotype and consequently, functions as a tumor suppressor in breast cancer. Runx1 ectopic expression in MCF10AT1 and MCF10CA1a BCa cells reduces (60%) migration, invasion and in vivo tumor growth in mouse mammary fat pad (P<0.05). Runx1 is decreased in BCSCs, and overexpression of Runx1 suppresses tumorsphere formation and reduces the BCSC population. Furthermore, Runx1 inhibits Zeb1 expression, while Runx1 depletion activates Zeb1 and the epithelial-mesenchymal transition. Mechanistically Runx1 functions as a tumor suppressor in breast cancer through repression of cancer stem cell activity. This key regulation of BCSCs by Runx1 may be shared in other epithelial carcinomas, highlighting the importance of Runx1 in solid tumors.

Sign in / Sign up

Export Citation Format

Share Document