scholarly journals Cylindromatosis Lysine 63 Deubiquitinase (CYLD) Regulates NF-kB Signaling Pathway and Modulates Fibroblast and Endothelial Cells Recruitment in Nasopharyngeal Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1924 ◽  
Author(s):  
Mingdan Deng ◽  
Wei Dai ◽  
Valen Zhuoyou Yu ◽  
Lihua Tao ◽  
Maria Li Lung
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Tumor Microenvironment ◽  
Signaling Pathway ◽  
Stromal Cell ◽  
Cell Infiltration ◽  
Functional Assays ◽  
The Impact

Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the nasopharynx. Cylindromatosis lysine 63 deubiquitinase (CYLD), a NF-kB inhibitor, was reported as one of the top mutated candidate genes in NPC. NF-kB is an inducible transcription factor, contributing to cancer via regulating inflammation, angiogenesis, cell proliferation, and metastasis. In this study, the impact of CYLD on regulating the NF-kB signaling pathway and its contribution to NPC development was studied using in vitro and in vivo functional assays, together with single cell RNA sequencing to understand the NPC tumor microenvironment. CYLD was downregulated in NPC clinical specimens and multiple cell lines. Functional assays revealed CYLD inhibits NPC cell proliferation and migration in vitro and suppresses NPC tumorigenicity and metastasis in vivo by negatively regulating the NF-kB signaling pathway. Additionally, CYLD was able to inhibit fibroblast and endothelial stromal cell infiltration into the NPC tumor microenvironment. These findings suggest that CYLD inhibits NPC development and provides strong evidence supporting a role for CYLD inhibiting fibroblast and endothelial stromal cell infiltration into NPC via suppressing the NF-kB pathway.

scholarly journals LINC00210 as a miR-328-5p sponge promotes nasopharyngeal carcinoma tumorigenesis by activating NOTCH3 pathway

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Shu Zhang ◽  
Ping Li ◽  
Lei Zhao ◽  
Ling Xu
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Untranslated Region ◽  
Poor Prognosis ◽  
Noncoding Rnas ◽  
Proliferation And Invasion

As a kind of essential regulators, long noncoding RNAs (lncRNAs) have attracted a lot of attention in recent years. Nevertheless, the function of lncRNA in nasopharyngeal carcinoma (NPC) remains poorly understood. In the present study, we explained the role and mechanism of LINC00210 in NPC progression. We found that LINC00210 expression was up-regulated in NPC samples. Besides, its overexpression was positively correlated with NPC metastasis while predicting poor prognosis. Based on functional experiments, we revealed that LINC00210 contributed to NPC cell proliferation and invasion in vitro, and promotes tumor growth in vivo. Mechanistically, we identified that LINC00210 was located in the cytoplasm of NPC cells and served as the miR-328-5p sponge. Furthermore, we showed that miR-328-5p targets the 3′ untranslated region (3′-UTR) of NOTCH3. Through inhibiting miR-328-5p activity, LINC00210 promoted NOTCH3 expression in NPC, leading to activation of NOTCH3 signaling pathway. In conclusion, our study indicates LINC00210 promotes NPC progression through modulating proliferation and invasion.

Silencing of MED27 inhibits adrenal cortical carcinogenesis by targeting the Wnt/β-catenin signaling pathway and the epithelial-mesenchymal transition process

2018 ◽  
Vol 399 (6) ◽  
pp. 593-602 ◽  
Author(s):  
Hongchao He ◽  
Jun Dai ◽  
Xiaoqun Yang ◽  
Xiaojing Wang ◽  
Fukang Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Transition Process ◽  
Tumor Xenograft ◽  
Mesenchymal Transition ◽  
Related Proteins ◽  
The Impact

AbstractThis study aimed to explore the effect ofMED27on the expression of epithelial-mesenchymal transition (EMT)-related proteins and β-catenin in adrenal cortical carcinoma (ACC). The functional mechanism ofMED27on ACC processes was also explored. The expression ofMED27was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). siRNA was utilized to knockdown the expression ofMED27. CCK8 assays were performed to evaluate SW-13 cell proliferation. Transwell assays were performed to assess the invasion ability, and wound healing assays were utilized to detect migration. A tumor xenograft mouse model was established to investigate the impact of silencingMED27on tumor growth and metastasis.MED27was highly expressed in ACC tissues and cells. Down-regulation ofMED27induced ACC cell apoptosis, and significantly attenuated ACC cell proliferation, invasion and metastasisin vivoandin vitro.MED27knockdown regulated the expression of EMT-related proteins and Wnt/β-catenin signaling pathway-related proteins. Our study investigated the function and mechanism ofMED27and validated thatMED27plays a negative role in ACC occurrence and progression and could be utilized as a new therapeutic target in ACC prevention and treatment.

scholarly journals Upregulation of Long Noncoding RNA_GAS5 Suppresses Cell Proliferation and Metastasis in Laryngeal Cancer via Regulating PI3K/AKT/mTOR Signaling Pathway

2021 ◽  
Vol 20 ◽  
pp. 153303382199007
Author(s):  
Wenlin Liu ◽  
Jiandong Zhan ◽  
Rong Zhong ◽  
Rui Li ◽  
Xiaoli Sheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Laryngeal Cancer ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Cancer Tissues ◽  
Lncrna Gas5

Background: Laryngeal cancer is one of the most common malignant tumors among head and neck cancers. Accumulating studies have indicated that long noncoding RNAs (lncRNAs) play an important role in laryngeal cancer occurrence and progression, however, the functional roles and relative regulatory mechanisms of lncRNA growth arrest-specific transcript 5 (GAS5) in laryngeal cancer progression remain unclear. Methods: The expression of lncRNA GAS5 in both laryngeal cancer tissues and cell lines was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. The relationships between lncRNA GAS5 expression and clinical parameters were also analyzed. To determine the biological function of lncRNA GAS5, a lncRNA GAS5-specific plasmid was first transfected into laryngeal cancer cells using lentiviral technology. Cell counting kit-8 assay, flow cytometry, and Transwell assays were used to detect in vitro cell proliferation, apoptosis, cycle distribution, and metastasis abilities, respectively. Furthermore, in vivo cell growth experiments were also performed using nude mice. Additionally, western blotting was performed to identify the underlying regulatory mechanism. Results: In the current study, lncRNA GAS5 was downregulated in laryngeal cancer tissues and its low expression was closely associated with poor tumor differentiation, advanced TNM stage, lymph node metastasis, and shorter overall survival time. In addition, lncRNA GAS5 upregulation significantly inhibited laryngeal cancer cell proliferation both in vitro and in vivo. Moreover, in response to lncRNA GAS5 overexpression, more laryngeal cancer cells were arrested at the G2/M stage, accompanied by increased cell apoptosis rates and suppressed migration and invasion capacities. Mechanistically, our data showed that the overexpression of lncRNA GAS5 significantly regulated the PI3K/AKT/mTOR signaling pathway. Conclusion: LncRNA GAS5 might act as a suppressor gene during laryngeal cancer development, as it suppressed cell proliferation and metastasis by regulating the PI3K/AKT/mTOR signaling pathway; thus, lncRNA GAS5 is a promising therapeutic biomarker for the treatment of laryngeal cancer.

scholarly journals HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/β-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor

2018 ◽  
Vol 19 (10) ◽  
pp. 3153 ◽  
Author(s):  
J. Muñoz-Bello ◽  
Leslie Olmedo-Nieva ◽  
Leonardo Castro-Muñoz ◽  
Joaquín Manzo-Merino ◽  
Adriana Contreras-Paredes ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Promote Cell Proliferation ◽  
E6 And E7 ◽  
Hpv 18

The Wnt/β-catenin signaling pathway regulates cell proliferation and differentiation and its aberrant activation in cervical cancer has been described. Persistent infection with high risk human papillomavirus (HR-HPV) is the most important factor for the development of this neoplasia, since E6 and E7 viral oncoproteins alter cellular processes, promoting cervical cancer development. A role of HPV-16 E6 in Wnt/β-catenin signaling has been proposed, although the participation of HPV-18 E6 has not been previously studied. The aim of this work was to investigate the participation of HPV-18 E6 and E6*I, in the regulation of the Wnt/β-catenin signaling pathway. Here, we show that E6 proteins up-regulate TCF-4 transcriptional activity and promote overexpression of Wnt target genes. In addition, it was demonstrated that E6 and E6*I bind to the TCF-4 (T cell factor 4) and β-catenin, impacting TCF-4 stabilization. We found that both E6 and E6*I proteins interact with the promoter of Sp5, in vitro and in vivo. Moreover, although differences in TCF-4 transcriptional activation were found among E6 intratype variants, no changes were observed in the levels of regulated genes. Furthermore, our data support that E6 proteins cooperate with β-catenin to promote cell proliferation.

scholarly journals SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Shiyu Chen ◽  
Zhonglin Jia ◽  
Ming Cai ◽  
Mujie Ye ◽  
Dandan Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Noncoding Rna ◽  
Chondrogenic Differentiation ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Tissue Sample ◽  
Human Umbilical Cord

Non-syndromic cleft lip and palate (NSCLP) is one of the most common congenital malformations with multifactorial etiology. Although long non-coding RNAs (lncRNAs) have been implicated in the development of lip and palate, their roles in NSCLP are not fully elucidated. This study aimed to investigate how dysregulated lncRNAs contribute to NSCLP. Using lncRNA sequencing, bioinformatics analysis, and clinical tissue sample detection, we identified that lncRNA ZFAS1 was significantly upregulated in NSCLP. The upregulation of ZFAS1 mediated by SP1 transcription factor (SP1) inhibited expression levels of Wnt family member 4 (WNT4) through the binding with CCCTC-binding factor (CTCF), subsequently inactivating the WNT/β-catenin signaling pathway, which has been reported to play a significant role on the development of lip and palate. Moreover, in vitro, the overexpression of ZFAS1 inhibited cell proliferation and migration in human oral keratinocytes and human umbilical cord mesenchymal stem cells (HUC-MSCs) and also repressed chondrogenic differentiation of HUC-MSCs. In vivo, ZFAS1 suppressed cell proliferation and numbers of chondrocyte in the zebrafish ethmoid plate. In summary, these results indicated that ZFAS1 may be involved in NSCLP by affecting cell proliferation, migration, and chondrogenic differentiation through inactivating the WNT/β-catenin signaling pathway.

Amplified LncRNA PVT1 promotes lung cancer proliferation and metastasis by facilitating VEGFC expression

2020 ◽  
Vol 98 (6) ◽  
pp. 676-682
Author(s):  
Yanming Pan ◽  
Lantao Liu ◽  
Yongxia Cheng ◽  
Jianbo Yu ◽  
Yukuan Feng
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Model ◽  
Cancer Proliferation ◽  
Survival Prognosis ◽  
Proliferation And Metastasis ◽  
Factor C ◽  
The Impact

Although the abundance of long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) in lung cancer has been well researched, the underlying mechanisms behind its effects were unknown. Here we investigated the molecular events regulating PVT1 in lung cancer. The pro-proliferative property of PVT1 was examined using a xenograft tumor model. Transwell chambers were used to analyze the impact of PVT1 expression on cell invasiveness and migration. In vivo metastasis was examined by tail-vein-injection in mice. Direct binding of miR-128 to PVT1 was investigated using a probe pulldown assay. The relative expression levels of miR-128 and PVT1 were quantified by real-time polymerase chain reaction and Western blotting. We show here that when PVT1 is amplified, there is a poor survival prognosis for patients with lung cancer. Elevated levels of PVT1 promoted lung cancer cell proliferation and metastasis, both in vitro and in vivo. Mechanistically, we found that PVT1 competes endogenously with miR-128 in the regulation of vascular endothelial growth factor C (VEGFC) expression, which is significantly associated with an unfavorable prognosis in lung cancer. We identified that copy number amplification significantly contributes to the high level of PVT1 transcripts in lung cancer, which promotes cell proliferation and metastatic behavior via modulating VEGFC expression by endogenous competition with miR-128.

scholarly journals Knockdown of Leptin Receptor Affects Macrophage Phenotype in the Tumor Microenvironment Inhibiting Breast Cancer Growth and Progression

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2078
Author(s):  
Luca Gelsomino ◽  
Giuseppina Daniela Naimo ◽  
Rocco Malivindi ◽  
Giuseppina Augimeri ◽  
Salvatore Panza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Leptin Receptor ◽  
Macrophage Phenotype ◽  
In Vivo Models ◽  
Monocyte Chemoattractant Protein 1 ◽  
Arginase 1 ◽  
The Impact

Aberrant leptin (Ob) signaling, a hallmark of obesity, has been recognized to influence breast cancer (BC) biology within the tumor microenvironment (TME). Here, we evaluated the impact of leptin receptor (ObR) knockdown in affecting BC phenotype and in mediating the interaction between tumor cells and macrophages, the most abundant immune cells within the TME. The stable knockdown of ObR (ObR sh) in ERα-positive and ERα-negative BC cells turned the tumor phenotype into a less aggressive one, as evidenced by in vitro and in vivo models. In xenograft tumors and in co-culture experiments between circulating monocytes and BC cells, the absence of ObR reduced the recruitment of macrophages, and also affected their cytokine mRNA expression profile. This was associated with a decreased expression and secretion of monocyte chemoattractant protein-1 in ObR sh clones. The loss of Ob/ObR signaling modulated the immunosuppressive TME, as shown by a reduced expression of programmed death ligand 1/programmed cell death protein 1/arginase 1. In addition, we observed increased phagocytic activity of macrophages compared to control Sh clones in the presence of ObR sh-derived conditioned medium. Our findings, addressing an innovative role of ObR in modulating immune TME, may open new avenues to improve BC patient health care.

scholarly journals EBV encoded miRNA BART8-3p promotes radioresistance in nasopharyngeal carcinoma by regulating ATM/ATR signaling pathway

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Xiaohan Zhou ◽  
Jialing Zheng ◽  
Ying Tang ◽  
Yanling lin ◽  
Lingzhi Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Ataxia Telangiectasia ◽  
Molecular Mechanisms ◽  
Radiation Treatment ◽  
Ataxia Telangiectasia Mutated ◽  
Barr Virus ◽  
Radiotherapy Resistance

Abstract Resistance to radiotherapy is one of the main causes of treatment failure in patients with nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) infection is an important factor in the pathogenesis of NPC, and EBV-encoded microRNAs (miRNAs) promote NPC progression. However, the role of EBV-encoded miRNAs in the radiosensitivity of NPC remains unclear. Here, we investigated the effects of EBV-miR-BART8-3p on radiotherapy resistance in NPC cells in vitro and in vivo, and explored the underlying molecular mechanisms. Inhibitors of ataxia telangiectasia mutated (ATM)/ataxia telangiectasia mutated and Rad3-related (ATR) (KU60019 and AZD6738, respectively) were used to examine radiotherapy resistance. We proved that EBV-miR-BART8-3p promoted NPC cell proliferation in response to irradiation in vitro and associated with the induction of cell cycle arrest at the G2/M phase, which was a positive factor for the DNA repair after radiation treatment. Besides, EBV-miR-BART8-3p could increase the size of xenograft tumors significantly in nude mice. Treatment with KU60019 or AZD6738 increased the radiosensitivity of NPC by suppressing the expression of p-ATM and p-ATR. The present results indicate that EBV-miR-BART8-3p promotes radioresistance in NPC by modulating the activity of ATM/ATR signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document