scholarly journals MicroRNA-296-5p inhibits cell metastasis and invasion in nasopharyngeal carcinoma by reversing transforming growth factor-β-induced epithelial–mesenchymal transition

2020 ◽  
Vol 25 (1) ◽  
Author(s):  
Meihui Chen ◽  
Chen Chen ◽  
Haiqing Luo ◽  
Jing Ren ◽  
Qiuqin Dai ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Real Time ◽  
Real Time Pcr ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Metastasis

Abstract Aim To explore the effect of miR-296-5p on the metastasis of nasopharyngeal carcinoma (NPC) cells and investigate the underlying mechanism. Methods The expressions of miR-296-5p in NPC tissues and cells were determined using GSE32920 database analysis and real-time PCR and miRNA microarray assays. An miR-296-5p mimic and inhibitor were transfected into NPC cells. Then, immunofluorescence imaging, scratch wound-healing, transwell migration and invasion assays were used to observe the effects of miR-296-5p on cell metastasis and invasion. Real-time PCR and western blotting were carried out to detect the expressions of genes and proteins related to epithelial–mesenchymal transition (EMT). A dual luciferase reporter assay was used to identify whether TGF-β is the target gene of miR-296-5p. Finally, TGF-β expression plasmids were transfected into NPC cells to verify the role of TGF-β in the miR-296-5p-mediated inhibition of nasopharyngeal carcinoma cell metastasis. Results Our results show that miR-296-5p inhibits the migratory and invasive capacities of NPC cells by targeting TGF-β, which suppresses EMT. Importantly, the miR-296-5p level was significantly lower in human NPC tissues than in adjacent normal tissues. It also negatively correlated with TGF-β and was significantly associated with the lymph node metastasis of patients with NPC. Conclusions Our findings show that miR-296-5p represses the EMT-related metastasis of NPC by targeting TGF-β. This provides new insight into the role of miR-296-5p in regulating NPC metastasis and invasiveness.

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 ZNRF3 Inhibits the Invasion and Tumorigenesis in Nasopharyngeal Carcinoma Cells by Inactivating the Wnt/β-Catenin Pathway

2017 ◽  
Vol 25 (4) ◽  
pp. 571-577 ◽  
Author(s):  
Zhongwei Wang ◽  
Yali Wang ◽  
Hongtao Ren ◽  
Yingying Jin ◽  
Ya Guo
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Ring Finger ◽  
Carcinoma Cells ◽  
Tumor Xenograft ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
And Function

Zinc and ring finger 3 (ZNRF3), which belongs to the E3 ubiquitin ligase family, is involved in the progression and development of cancer. However, the expression and function of ZNRF3 in human nasopharyngeal carcinoma (NPC) remain unclear. Thus, the aim of this study was to investigate the role of ZNRF3 in human NPC. Our results showed that ZNRF3 was downregulated in NPC cell lines. Restoration of ZNRF3 significantly inhibited the proliferation of NPC cells and tumor xenograft growth in vivo. In addition, overexpression of ZNRF3 suppressed migration and invasion, as well as attenuated the epithelial‐mesenchymal transition (EMT) process in NPC cells. Furthermore, restoration of ZNRF3 obviously downregulated the expression levels of β-catenin, cyclin D1, and c-Myc in NPC cells. In conclusion, these data suggest that ZNRF3 inhibited the metastasis and tumorigenesis via suppressing the Wnt/β-catenin signaling pathway in NPC cells. Thus, ZNRF3 may act as a novel molecular target for the treatment of NPC.

scholarly journals Circ_001569 regulates FLOT2 expression to promote the proliferation, migration, invasion and EMT of osteosarcoma cells through sponging miR-185-5p

2020 ◽  
Vol 15 (1) ◽  
pp. 476-487
Author(s):  
Bin Xiao ◽  
Xusheng Zhang ◽  
Xiaojuan Li ◽  
Zhipeng Zhao
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
New Approach ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis ◽  
Related Proteins

AbstractOsteosarcoma (OS) is a common malignant tumor in the world. Circular RNAs are endogenous non-coding RNAs that have been linked to the development of cancer. However, the role of circ_001569 in OS progression is still unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_001569, microRNA-185-5p (miR-185-5p) and flotillin-2 (FLOT2). The abilities of cell proliferation, migration and invasion were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays, respectively. Also, western blot analysis was performed to assess the levels of epithelial–mesenchymal transition (EMT)-related proteins and FLOT2 protein. Besides, the dual-luciferase reporter assay was used to verify the interactions among circ_001569, miR-185-5p and FLOT2. Circ_001569 expression was increased in OS tissues and cells, and its knockdown reduced the proliferation, migration, invasion and EMT of OS cells. MiR-185-5p could interact with circ_001569. Inhibition of miR-185-5p could recover the suppression effects of silenced-circ_001569 on the proliferation and metastasis of OS cells. Furthermore, FLOT2 was a target of miR-185-5p. Overexpressed FLOT2 could restore the inhibition effects of miR-185-5p mimic on the proliferation and metastasis of OS cells. Also, FLOT2 expression was regulated by circ_001569 and miR-185-5p. In addition, circ_001569 knockdown also reduced the OS tumor growth in vivo. Circ_001569 might act as an oncogene in OS progression by regulating the miR-185-5p/FLOT2 axis, which provided a reliable new approach for the treatment of OS patients.

scholarly journals Ginsenoside Rg3 Inhibits Migration and Invasion of Nasopharyngeal Carcinoma Cells and Suppresses Epithelial Mesenchymal Transition

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Dingkun Wang ◽  
Cheng Wu ◽  
Dongbo Liu ◽  
Linli Zhang ◽  
Guoxian Long ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Carcinoma Cells ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Ginsenoside Rg3 ◽  
Antitumor Effects ◽  
Mesenchymal Transition ◽  
Marker Proteins

Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic head and neck cancer. Distant metastasis becomes the predominant mode of treatment failure in NPC patients. Ginsenoside Rg3 (Rg3), an active pharmaceutical component extracted from traditional Chinese medicine ginseng, shows antitumor effects in various cancers. In this study, we aimed to determine whether Rg3 inhibits the migration and invasion activity of NPC cells and to explore the possible mechanisms. Our results revealed that Rg3 hampers cell migration and invasion in both HNE1 and CNE2 cell lines. A reduced level of matrix metalloproteinase-2 (MMP-2) and MMP-9 was induced by Rg3 treatment. In addition, Rg3 significantly altered the expression of epithelial mesenchymal transition (EMT) markers with increased E-cadherin but decreased Vimentin and N-cadherin expression. Transforming growth factorβ- (TGF-β-) induced morphological transition and marker proteins change of EMT were reversed by Rg3. What is more, Rg3 suppressed the expression of EMT-related transcription factors, especially the Zinc Finger E-Box Binding Homeobox 1 (ZEB1). In summary, our data suggested that Rg3 could inhibit migration and invasion of NPC cells. This effect of Rg3 might be mediated through regulating MMP-2 and MMP-9 expressions and suppressing EMT. Thus, Rg3 may be a potentially effective agent for the treatment of NPC.

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 Upregulation of circRNA hsa_circ_0008726 in Pre-eclampsia Inhibits Trophoblast Migration, Invasion, and EMT by Regulating miR-345-3p/RYBP Axis

2021 ◽  
Author(s):  
Chang Shu ◽  
Peng Xu ◽  
Jun Han ◽  
Shumei Han ◽  
Jin He
Keyword(s):  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Extravillous Trophoblast ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Rnase R ◽  
Mesenchymal Transition ◽  
Potential Biomarker ◽  
Rna Immunoprecipitation

AbstractAccumulating evidence shows that impaired spiral artery remodeling, placental dysfunction, and insufficient trophoblast infiltration contribute to the etiology and pathogenesis of pre-eclampsia (PE). circRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many diseases, including PE. This study aims to investigate the role of circRNA hsa_circ_0008726 in regulating the migration and invasion of extravillous trophoblast cells. RNase R assay was performed to confirm that circ_0008726 was a circular transcript. The expression of circ_0008726, RYBP, and miR-345-3p was examined by qRT-PCR. The functional interaction between miR-345-3p and circ_0008726 or RYBP was confirmed using dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Cell migration and invasion ability was analyzed by Transwell assays. Western blot was used for the quantification of RYBP protein level. Circ_0008726 expression was significantly increased in PE placenta tissues as compared with normal placenta tissues. Circ_0008726 was resistant to RNase R digestion and was predominately located in the cytoplasm of HTR-8/SVneo cells. Silencing circ_0008726 promoted cell migration and EMT (epithelial-mesenchymal transition), while circ_0008726 overexpression suppressed these processes. Mechanistically, circ_0008726 sponged miR-345-3p to negatively regulate its expression, and miR-345-3p negatively modulated the expression of RYBP. In PE samples, the expression level of circ_0008726 was negatively correlated with miR-345-3p level, but was positively correlated with RYBP expression. Transfection of miR-345-3p mimic or RYBP knockdown counteracted the effects of circ_0008726 overexpression on cell migration and EMT. Our data demonstrate the upregulation of circ_0008726 in PE placenta, which inhibits the migration, invasion, and EMT of HTR-8/SVneo cells by targeting miR-345-3p/RYBP axis. These data suggest that circ_0008726 could be a potential biomarker and therapeutic target for PE.

scholarly journals LncRNA DHRS4-AS1 Inhibits the Stemness of NSCLC Cells by Sponging miR-224-3p and Upregulating TP53 and TET1

2020 ◽  
Vol 8 ◽  
Author(s):  
Fei Yan ◽  
Wei Zhao ◽  
Xiaoyue Xu ◽  
Chenchen Li ◽  
Xiaoyou Li ◽  
...  
Keyword(s):  
Real Time ◽  
Cancer Cell ◽  
Real Time Pcr ◽  
Colony Formation ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Related Factors ◽  
Mesenchymal Transition

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death. This study aimed to examine the roles of DHRS4-AS1/miR-224-3p signaling in the cancer cell stemness of NSCLC. Real-time PCR showed that DHRS4-AS1 was downregulated in cancerous tissues, and bioinformatics analysis revealed that high DHRS4-AS1 expression indicated a good prognosis for NSCLC patients. Sphere and colony formation assays showed that DHRS4-AS1 overexpression significantly suppressed NSCLC cell colony formation and stem cell-like properties. DHRS4-AS1 also abrogated the expression of OCT4, SOX2, CD34, and CD133, markedly inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors, N-cadherin, ZEB1, and Vimentin, and increased E-cadherin expression in spheres. Furthermore, luciferase reporter assays and real-time PCR analysis demonstrated that DHRS4-AS1 and miR-224-3p were antagonistically repressed in NSCLC cells. RNA immunoprecipitation (RIP) analysis revealed that DHRS4-AS1 interacted with miR-224-3p. DHRS4-AS1 partially reversed the miR-224-3p-decreased TP53 and TET1, resulting in the inhibition of tumor growth in vivo. Finally, TP53 and TET1 were antagonistically regulated by DHRS4-AS1 and miR-224-3p in NSCLC cells. In conclusion, TP53- and TET1-associated DHRS4-AS1/miR-224-3p axis is an essential mechanism by which NSCLC modulates cancer cell stemness.

scholarly journals Long noncoding RNA NEAT1 aggravates osteosarcoma carcinogenesis via regulating the microRNA-579/MMP13 axis

2020 ◽  
Author(s):  
Lili Wang ◽  
Jingzhen Zhou ◽  
Yong Zhang ◽  
Tao Hu ◽  
Yongning Sun
Keyword(s):  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Gene Assay ◽  
Lncrna Neat1

Abstract Background: Previous studies have suggested that long non-coding RNAs (lncRNAs) were involved in tumorigenesis in various human carcinomas, including osteosarcoma (OS). However, the expression and specific role of lncRNA NEAT1 in OS remain unknown. The current study aimed at revealing the role of lncRNA NEAT1 and its related mechanism in OS.Methods: Expression profiles of lncRNAs in OS tissues were constructed, and lncRNA NEAT1 expression was verified with RT-qPCR followed by sub-localization. LncRNA-microRNA (miRNA) and miRNA-mRNA interactions were predicted. Validation was performed using dual luciferase reporter gene assay, and gain- and loss-of-function experiments. The effects of lncRNA NEAT1, miR-579 and MMP13 on the proliferation, migration and invasion, epithelial-mesenchymal transition (EMT) of OS cells were detected using colony formation, cell counting kit-8 (CCK-8), Transwell assays and Western blot analysis.Results: LncRNA NEAT1 overexpression was observed in OS tissues and cell lines which located in the cytoplasm. Transfection-induced downregulation of lncRNA NEAT1/MMP13 or overexpression of miR-579 blocked the progression of OS cells. LncRNA NEAT1 promotes MMP13 through sponging miR-579.Conclusion: LncRNA NEAT1 might be beneficial for OS aggravation via sponging miR-579 and facilitating MMP13 expression, which represents a candidate marker and target for OS therapy.

scholarly journals miR-22 Suppresses Epithelial-Mesenchymal Transition by Modulating Snail and MAPK1 in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Cheng-Gong Liao ◽  
Zhi Qu ◽  
Zao-Xia Guo ◽  
Xiao-Hua Liang ◽  
Ling-Min Kong
Keyword(s):  
Real Time ◽  
Epithelial Mesenchymal Transition ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Rt Pcr ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Mitogen Activated Protein ◽  
Emt Markers

Abstract Background: Recently studies have reported that miR-22 plays an important role in epithelial-mesenchymal transition (EMT) of many human cancers. However, the involvement of miR-22 in hepatocellular carcinomas (HCC) EMT progression has not been investigated. Methods: We measured miR-22 expression level in 38 paired of HCC and matched normal tissues by real-time quantitative RT-PCR. Then, we performed morphological analysis and immunofluorescence to observe the role of miR-22 in HCC EMT progression. The expression of EMT markers were detected by real-time RT-PCR and western blot. The regulation role of miR-22 on Snail, mitogen-activated protein kinase 1(MAPK1) and slug were determined by luciferase reporter assay. The expression of Snail and MAPK1 were also detected by real-time quantitative RT-PCR in HCC and normal tissues. Results: We found that the expression of miR-22 in HCC tissues were much lower than that in normal control. The expression of miR-22 was inversely correlated with HCC metastatic ability. Then, we found that overexpression of miR-22 could inhibit HCC EMT. Importantly, miR-22 is found to inhibit cell motility by directly targeting both Snail and MAPK1. Furthermore, the suppression role of miR-22 in HCC EMT could be blocked by Snail and MAPK1 overexpression. Additionally, the expression of Snail and MAPK1 were inversely correlated with miR-22 expression in HCC tissues. Conclusion: Our results suggested that miR-22 was downexpressed in HCC tissues and inhibited HCC EMT through downregulating Snail and MAPK1 which may provide a new bio-target for HCC therapy.

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.

Sign in / Sign up

Export Citation Format

Share Document