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.

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.

scholarly journals Long non-coding RNA LINC00152 promotes gallbladder cancer metastasis and epithelial–mesenchymal transition by regulating HIF-1α via miR-138

Open Biology ◽  
2017 ◽  
Vol 7 (1) ◽  
pp. 160247 ◽  
Author(s):  
Qiang Cai ◽  
Zhenqiang Wang ◽  
Shouhua Wang ◽  
Mingzhe Weng ◽  
Di Zhou ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Hepatocellular Cancer ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Long non-coding RNA LINC00152 had been reported as an oncogene in gastric and hepatocellular cancer. In this study, we show that LINC00152 is overexpressed in gallbladder cancer (GBC) tissue samples and cell lines. The high LINC00152 levels correlated negatively with the overall survival time in GBC patients. Functionally, LINC00152 dramatically promoted cell migration, invasion and epithelial–mesenchymal transition (EMT) progression in vitro. In vivo , LINC00152 overexpression significantly promoted tumour peritoneal spreading and metastasis. Mechanistic analyses indicated that LINC00152 functions as a molecular sponge for miR-138, which directly suppresses the expression of hypoxia inducible factor-1α (HIF-1α). We revealed that miR-138 is a suppressor of GBC cell metastasis and EMT progression, and a similar phenomenon was observed in HIF-1α knockdown NOZ cells. Through binding to miR-138, LINC00152 has an oncogenic effect on GBC. Overall, our study suggested that the LINC00152/miR-138/HIF-1α pathway potentiates the progression of GBC, and LINC00152 may be a novel therapeutic target.

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.

scholarly journals LncRNA FBXL19-AS1 promotes proliferation and metastasis of cervical cancer through upregulating COL1A1 as a sponge of miR-193a-5p

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Xiaoyong Huang ◽  
Haiyan Shi ◽  
Xinghai Shi ◽  
Xuemei Jiang
Keyword(s):  
Cervical Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Proliferation And Metastasis ◽  
Leucine Rich Repeat Protein ◽  
Competitive Endogenous Rna

Abstract Background Cervical cancer (CC) is one of the most common and malignant tumors in women. In this study, we aim to explore the role and mechanism of F-box and leucine rich repeat protein 19 antisense RNA 1 (FBXL19-AS1), a novel long-chain non coding RNA (lncRNA) with marked roles in a variety of tumors, in regulating the proliferation and metastasis of CC. Methods The expression of FBXL19-AS1, miR-193a-5p and COL1A1 were detected by RT-PCR and western blot. Gain- and loss-of functional assays of FBXL19-AS1 and miR-193a-5p were performed in CC cell lines in vitro or in vivo. The proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT) of CC cells were determined. Results FBXL19-AS1 and COL1A1 were significantly up-regulated in CC tissues, while miR-193a-5p was significantly down-regulated. Overexpression of FBXL19-AS1 significantly promoted the proliferation, migration, invasion, EMT and growth of CC cells and inhibited apoptosis, while knockdown of FBXL19-AS1 had the opposite effects. On the other hand, miR-193a-5p inhibited the proliferation and metastasis of CC cells. Mechanistically, FBXL19-AS1 functioned as a competitive endogenous RNA (ceRNA) and inhibited the expression of miR-193a-5p, which targeted at the 3’-UTR site of COL1A1 and negatively regulated COL1A1 expression. Conclusions FBXL19-AS1 promotes the proliferation and metastasis of CC cells by sponging miR-193a-5p and up-regulating COL1A1.

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.

scholarly journals O-GlcNAc modified-TIP60/KAT5 is required for PCK1 deficiency-induced HCC metastasis

Oncogene ◽  
2021 ◽  
Author(s):  
Rui Liu ◽  
Dongmei Gou ◽  
Jin Xiang ◽  
Xuanming Pan ◽  
Qingzhu Gao ◽  
...  
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Epithelial Mesenchymal Transition ◽  
Hepatoma Cell ◽  
Metabolic Enzyme ◽  
Loss Of Function ◽  
Post Translational Modification ◽  
Mesenchymal Transition ◽  
Histone H4 Acetylation

AbstractAberrant glucose metabolism and elevated O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) are hallmarks of hepatocellular carcinoma (HCC). Loss of phosphoenolpyruvate carboxykinase 1 (PCK1), the major rate-limiting enzyme of hepatic gluconeogenesis, increases hexosamine biosynthetic pathway (HBP)-mediated protein O-GlcNAcylation in hepatoma cell and promotes cell growth and proliferation. However, whether PCK1 deficiency and hyper O-GlcNAcylation can induce HCC metastasis is largely unknown. Here, gain- and loss-of-function studies demonstrate that PCK1 suppresses HCC metastasis in vitro and in vivo. Specifically, lysine acetyltransferase 5 (KAT5), belonging to the MYST family of histone acetyltransferases (HAT), is highly modified by O-GlcNAcylation in PCK1 knockout hepatoma cells. Mechanistically, PCK1 depletion suppressed KAT5 ubiquitination by increasing its O-GlcNAcylation, thereby stabilizing KAT5. KAT5 O-GlcNAcylation epigenetically activates TWIST1 expression via histone H4 acetylation, and enhances MMP9 and MMP14 expression via c-Myc acetylation, thus promoting epithelial-mesenchymal transition (EMT) in HCC. In addition, targeting HBP-mediated O-GlcNAcylation of KAT5 inhibits lung metastasis of HCC in hepatospecific Pck1-deletion mice. Collectively, our findings demonstrate that PCK1 depletion increases O-GlcNAcylation of KAT5, epigenetically induces TWIST1 expression and promotes HCC metastasis, and link metabolic enzyme, post-translational modification (PTM) with epigenetic regulation.

scholarly journals Silencing of Long Non-Coding RNA LINC00607 Prevents Tumor Proliferation of Osteosarcoma by Acting as a Sponge of miR-607 to Downregulate E2F6

2021 ◽  
Vol 10 ◽  
Author(s):  
Yuehuan Zheng ◽  
Zhe Chen ◽  
Zezhu Zhou ◽  
Xiangyang Xu ◽  
Huilin Yang
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Bioinformatic Analysis ◽  
Transcriptional Factor ◽  
Migration And Invasion ◽  
Tumor Proliferation ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Osteosarcoma (OS), a type of malignant bone tumor, is commonly found in children and adolescents. Although previous studies have identified that long non-coding RNAs (lncRNAs) regulate OS, it is unclear whether lncRNAs impact the progression of OS. Here, we identified LINC00607, a lncRNA that facilitates OS proliferation, migration, and invasion. Based on the RNA-sequencing results, LINC00607 expression was significantly upregulated in pulmonary metastasis within OS. Functional experiments revealed that LINC00607 promoted migration and invasion of endothelial cells to exacerbate epithelial-mesenchymal transition (EMT). Furthermore, the results of RNA pull-down assay and invasion assay suggested that the binding between LINC00607 and miR-607 promoted OS invasion. Bioinformatic analysis and rescue experiments demonstrated that E2F6, a transcriptional factor, functioned downstream of LINC00607/miR-607. Finally, we found that LINC00607 promoted OS progression in vivo. This work revealed that LINC00607 worked as an miR-607 sponge to upregulate E2F6 expression, which promoted tumor proliferation in OS. These results identified a novel therapeutic target for treating OS.

scholarly journals Downregulation of SLC27A6 by DNA Hypermethylation Promotes Proliferation but Suppresses Metastasis of Nasopharyngeal Carcinoma Through Modulating Lipid Metabolism

2022 ◽  
Vol 11 ◽  
Author(s):  
Xuemin Zhong ◽  
Yanping Yang ◽  
Bo Li ◽  
Pan Liang ◽  
Yiying Huang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Nasopharyngeal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Promoter Hypermethylation ◽  
Migration And Invasion ◽  
Dna Hypermethylation ◽  
Mesenchymal Transition

Lipid is the building block and an important source of energy, contributing to the malignant behavior of tumor cells. Recent studies suggested that lipid droplets (LDs) accumulations were associated with nasopharyngeal carcinoma (NPC) progression. Solute carrier family 27 member 6 (SLC27A6) mediates the cellular uptake of long-chain fatty acid (LCFA), a necessary lipid component. However, the functions of SLC27A6 in NPC remain unknown. Here, we found a significant reduction of SLC27A6 mRNA in NPC tissues compared with normal nasopharyngeal epithelia (NNE). The promoter methylation ratio of SLC27A6 was greater in NPC than in non-cancerous tissues. The demethylation reagent 5-aza-2’-deoxycytidine (5-aza-dC) remarkably restored the mRNA expression of SLC27A6, suggesting that this gene was downregulated in NPC owing to DNA promoter hypermethylation. Furthermore, SLC27A6 overexpression level in NPC cell lines led to significant suppression of cell proliferation, clonogenicity in vitro, and tumorigenesis in vivo. Higher SLC27A6 expression, on the other hand, promoted NPC cell migration and invasion. In particular, re-expression of SLC27A6 faciliated epithelial-mesenchymal transition (EMT) signals in xenograft tumors. Furthermore, we observed that SLC27A6 enhanced the intracellular amount of triglyceride (TG) and total cholesterol (T-CHO) in NPC cells, contributing to lipid biosynthesis and increasing metastatic potential. Notably, the mRNA level of SLC27A6 was positively correlated with cancer stem cell (CSC) markers, CD24 and CD44. In summary, DNA promoter hypermethylation downregulated the expression of SLC27A6. Furthermore, re-expression of SLC27A6 inhibited the growth capacity of NPC cells but strengthened the CSC markers. Our findings revealed the dual role of SLC27A6 in NPC and shed novel light on the link between lipid metabolism and CSC maintenance.

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.

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