The Integrated Analysis of Differential Long Non-Coding RNAs Expression Profiles in Extracellular Vesicles Derived From Chemoradioresistant and Parental Nasopharyngeal Carcinoma Cells

Abstract The patients with nasopharyngeal carcinoma (NPC) suffer from poor outcomes after chemoradiotherapy. Extracellular vesicles (EVs) play crucial roles in regulating cancer progression and chemoradioresistance. To investigate the functional role of chemoradioresistant cell-derived EVs for parental cells, and long non-coding RNAs (lncRNAs) expression profiles in EVs secreted by chemoradioresistant cells. The effect of chemoradioresistant NPC cell-derived EVs on migration and invasion abilities of parental cells were detected by Transwell assays. Human cancer lncRNA PCR array was performed on EVs released from chemoradioresistant NPC cells (CNE1R and CNE2R) and parental cells (CNE1 and CNE2). The concurrent chemoradioresistance of CNE1R and CNE2R was significant higher than that of CNE1 and CNE2. Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blotting results showed the CNE1, CNE2, CNE1R and CNE2R -derived EVs were successfully obtained. The chemoradioresistant cell-derived EVs remarkably promoted migration and invasion ability of parental cells with different differentiation. Notably, a total of 91 differentially expressed (DE) lncRNAs were regulated in EVs by chemoradiotherapy. Among them, the 4 upregulated (MALAT1, FAM212B-AS1, LINC-PINT and H19) and 7 down-regulated (SNHG16, CDKN2B-AS1, ZFAS1, CCAT1, SNHG6, GAPLINC and TUG1) DE lncRNAs associated with chemoradioresistance, were identified in EVs derived from chemoradioresistant cells with different differentiation. We found the EVs derived from chemoradioresistant NPC cells regulated an aggressive phenotype of NPC cells, and identified an altered lncRNAs expression pattern in chemoradioresistant NPC cell- derived EVs.

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Integrated Analysis of Long Non-Coding RNA and mRNA Expression Profiles in Testes of Calves and Sexually Mature Wandong Bulls (Bos taurus)

Animals ◽

10.3390/ani11072006 ◽

2021 ◽

Vol 11 (7) ◽

pp. 2006

Author(s):

Hongyu Liu ◽

Ibrar Muhammad Khan ◽

Huiqun Yin ◽

Xinqi Zhou ◽

Muhammad Rizwan ◽

...

Keyword(s):

Target Genes ◽

Expression Profiles ◽

Age Groups ◽

Adherens Junction ◽

Integrated Analysis ◽

Sequencing Data ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Rna Interaction ◽

Long Non Coding Rna

The mRNAs and long non-coding RNAs axes are playing a vital role in the regulating of post-transcriptional gene expression. Thereby, elucidating the expression pattern of mRNAs and long non-coding RNAs underlying testis development is crucial. In this study, mRNA and long non-coding RNAs expression profiles were investigated in 3-month-old calves and 3-year-old mature bulls’ testes by total RNA sequencing. Additionally, during the gene level analysis, 21,250 mRNAs and 20,533 long non-coding RNAs were identified. As a result, 7908 long non-coding RNAs (p-adjust < 0.05) and 5122 mRNAs (p-adjust < 0.05) were significantly differentially expressed between the distinct age groups. In addition, gene ontology and biological pathway analyses revealed that the predicted target genes are enriched in the lysine degradation, cell cycle, propanoate metabolism, adherens junction and cell adhesion molecules pathways. Correspondingly, the RT-qPCR validation results showed a strong consistency with the sequencing data. The source genes for the mRNAs (CCDC83, DMRTC2, HSPA2, IQCG, PACRG, SPO11, EHHADH, SPP1, NSD2 and ACTN4) and the long non-coding RNAs (COX7A2, COX6B2, TRIM37, PRM2, INHBA, ERBB4, SDHA, ATP6VOA2, FGF9 and TCF21) were found to be actively associated with bull sexual maturity and spermatogenesis. This study provided a comprehensive catalog of long non-coding RNAs in the bovine testes and also offered useful resources for understanding the differences in sexual development caused by the changes in the mRNA and long non-coding RNA interaction expressions between the immature and mature stages.

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Long Non-Coding RNA-DUXAP8 Regulates TOP2A in the Growth and Metastasis of Osteosarcoma via MicroRNA-635

10.21203/rs.3.rs-77487/v1 ◽

2020 ◽

Author(s):

Ting Yang ◽

Jian Ping Quo ◽

Fan Li ◽

Chao Xiu ◽

Hua Wang ◽

...

Keyword(s):

Cancer Progression ◽

Human Cancer ◽

Luciferase Reporter ◽

Migration And Invasion ◽

High Morbidity ◽

Real Time Quantitative Pcr ◽

Diagnosis And Prognosis ◽

Non Coding Rna ◽

Cell Progression ◽

And Migration

Abstract Purpose: Osteosarcoma (OS) is a malignant tumor disease with high morbidity and mortality in children and adolescents. Evidence indicates that long non-coding RNAs (lncRNAs) may be important players in human cancer progression, including OS. In this study, we identified the role of lnc-DUXAP8 in the development of OS.Materials and Methods: Expression of lncRNA DUXAP8 was determined by real-time quantitative PCR and Western blotting in OS tissues. Cell proliferation was evaluated using CCK8 and colony formation assay; Transwell assay was conducted to measure cell invasion. Cell migration was evaluated using Wound Healing assay. The binding site between the lnc-DUXAP8 and miR-635 RNAs was evaluated using a luciferase reporter assay. Results: The expression of the lnc-DUXAP8 was significantly upregulated in OS samples and OS cell lines compared to normal tissue. High expression of lncRNA DUXAP8 was associated with shorter overall survival. Knockdown of lncRNA DUXAP8 inhibited proliferation and migration, and invasion in OS cells. More importantly, mechanism investigation revealed that lncRNA DUXAP8 was predominantly acted as a competing endogenous RNA (ceRNA) in OS by regulating miR-635/ TOP2A axis. Conclusion: LncRNA DUXAP8 is upregulated in OS, and LncRNA DUXAP8 knockdown plays a vital anti-tumor role in OS cell progression through a miR-635/ TOP2A axis. Our study suggests that LncRNA DUXAP8 may be a novel, promising biomarker for diagnosis and prognosis of OS.

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Dysregulation of miRNA in cancer progression

10.31219/osf.io/u429y ◽

2021 ◽

Author(s):

Rucha P.

Keyword(s):

Gene Regulation ◽

Cancer Progression ◽

Therapeutic Target ◽

Chromosomal Abnormalities ◽

Human Cancer ◽

Epigenetic Modification ◽

Therapeutic Applications ◽

Non Coding Rnas ◽

Transcriptional Gene Regulation

MicroRNAs (miRNAs) are a category of highly conserved tiny non-coding RNAs that play a role in post-transcriptional gene regulation. Numerous studies have shown the role of dysregulated miRNA in a variety of illnesses, including human cancer. MiRNA is dysregulated by a variety of processes, including dysregulation of miRNA synthesis, aberrant miRNA transcription, dysregulated epigenetic modification, and chromosomal abnormalities. MiRNAs that are overexpressed have been shown to influence cancer's hallmarks. Recent research has shown miRNA's potential as a therapeutic target and biomarker. In this review, we discussed the synthesis and regulation of miRNA, as well as its dysregulation in human cancer and other disorders, as well as some of the therapeutic applications of miRNA.

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Integrated analysis profiles of long non–coding RNAs reveal potential biomarkers across brain regions in post–traumatic stress disorder

10.21203/rs.3.rs-15824/v1 ◽

2020 ◽

Author(s):

Yaoyao Bian ◽

Lili Yang ◽

Zhongli Wang ◽

Wen Li ◽

Qing Wang ◽

...

Keyword(s):

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Expression Profiles ◽

Differentially Expressed ◽

Integrated Analysis ◽

Post Traumatic Stress ◽

Post Traumatic ◽

Non Coding Rnas ◽

Potential Biomarkers

Abstract Background Post–traumatic stress disorder (PTSD) is characterized by impaired fear extinction, excessive anxiety and depression. However, underlying mechanisms, especially the function roles of long non–coding RNAs (lncRNAs) involved in PTSD is still unclear. We argued that the lncRNAs, co–expressed mRNAs, as well as the associated pathways, are altered and may thus serve as potential biomarkers and key pathways related to PTSD.Methods The gene expression profiles of GSE68077 was downloaded from the GEO database, and the differentially expressed lncRNAs and mRNAs were identified. Gene ontology (GO) and Kyto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis were performed. Subsequently, protein–protein interaction (PPI) network was analyzed, and module analysis of the differentially expressed mRNAs was performed with Cytoscape software. Finally, lncRNAs–mRNAs co–expression network was constructed and core pair lncRNAs involved in PTSD were mapped.Results A total of 45 differentially expressed lncRNAs and 726 differentially expressed mRNAs were obtained. Among of which, 17 lncRNAs and 86 mRNAs were inter–regulated, and most of the lncRNAs–mRNAs co–expression showed positive correlations. The lncRNAs–mRNAs co–expressed network suggested the potentially functional roles of lncRNAs, regulated mRNAs and related pathways in PTSD. By implication of the core pair network, lncRNA–NONMMUT010120.2 synergistically up–regulated Ppargc1a and down–regulated Cir1, Slc38a9, Atp6v0a2. Moreover, lncRNA–NONMMUT023440.2, NONMMUT034155.2, NONMMUT105407.1 and NONMMUT149972.1 were co–expressed with 10 co–expressed mRNAs, which indicated that lncRNAs involved in PTSD might work by regulating the co–expressed mRNAs.

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Gastric Cancer Extracellular Vesicles Tune the Migration and Invasion of Epithelial and Mesenchymal Cells in a Histotype-Dependent Manner

International Journal of Molecular Sciences ◽

10.3390/ijms20112608 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2608 ◽

Cited By ~ 3

Author(s):

Sara Rocha ◽

Sara Pinto Teles ◽

Mafalda Azevedo ◽

Patrícia Oliveira ◽

Joana Carvalho ◽

...

Keyword(s):

Gastric Cancer ◽

Flow Cytometry ◽

Tumor Microenvironment ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Mesenchymal Cells ◽

Migration And Invasion ◽

Dependent Manner ◽

Diffuse Type ◽

Transmission Electron

Extracellular vesicles (EVs) secreted by tumor cells modulate recipient cells’ behavior, but their effects in normal cells from the tumor microenvironment remain poorly known. In this study, we dissected the functional impact of gastric cancer cell-derived EVs (GC-EVs), representative of distinct GC histotypes, on the behavior of normal isogenic epithelial and mesenchymal cells. GC-EVs were isolated by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and imaging flow-cytometry. Epithelial and mesenchymal cells were challenged with GC-EVs and submitted to proliferation, migration, and invasion assays. Expression of epithelial and mesenchymal markers was followed by immunofluorescence and flow-cytometry. Our results indicated that GC-EVs secreted by diffuse-type cancer cells decrease the migration of recipient cells. This effect was more prominent and persistent for mesenchymal recipient cells, which also increased Fibronectin expression in response to EVs. GC-EVs secreted by cancer cells derived from tumors with an intestinal component increased invasion of recipient epithelial cells, without changes in EMT markers. In summary, this study demonstrated that GC-EVs modulate the migration and invasion of epithelial and mesenchymal cells from the tumor microenvironment, in a histotype-dependent manner, highlighting new features of intestinal and diffuse-type GC cells, which may help explaining differential metastasis patterns and aggressiveness of GC histotypes.

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MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma

Cell Death and Disease ◽

10.1038/s41419-019-2060-9 ◽

2019 ◽

Vol 10 (11) ◽

Cited By ~ 8

Author(s):

ShiJuan Mai ◽

RuoWen Xiao ◽

Lu Shi ◽

XiaoMin Zhou ◽

Te Yang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cancer Progression ◽

Ectopic Expression ◽

Mtor Pathway ◽

Migration And Invasion ◽

Clinical Samples ◽

Antitumor Effects ◽

Barr Virus ◽

Epstein Barr

Abstract miR-18a has been reported to be upregulated in nasopharyngeal carcinoma (NPC) tissues by microarray assays. However, the roles and the underlying mechanisms of miR-18a in NPC remain poorly understood. Here we demonstrated by real-time RT-PCR that miR-18a expression is upregulated in NPC tissues, and positively correlated with tumor size and TNM stage. Moreover, miR-18a expression could be upregulated by NF-κB activation or Epstein-Barr virus encoded latent membrane protein 1 expression. The ectopic expression of miR-18a promoted NPC cell proliferation, migration and invasion, while the repression of miR-18a had opposite effects. Candidate genes under regulation by miR-18a were screened out through a whole-genome microarray assay, further identified by a reporter assay and verified in clinical samples. SMG1, a member of the phosphoinositide 3-kinase-related kinases family and an mTOR antagonist, was identified as functional target of miR-18a. Our results confirmed that miR-18a exerts its oncogenic role through suppression of SMG1 and activation of mTOR pathway in NPC cells. Importantly, in vivo xenograft tumor growth in nude mice was effectively inhibited by intratumor injection of miR-18a antagomir. Our data support an oncogenic role of miR-18a through a novel miR-18a/SMG1/mTOR axis and suggest that the antitumor effects of antagomir-18a may make it suitable for NPC therapy.

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Microenvironmental Hypoxia Induces Dynamic Changes in Lung Cancer Synthesis and Secretion of Extracellular Vesicles

Cancers ◽

10.3390/cancers12102917 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2917

Author(s):

Shun Wilford Tse ◽

Chee Fan Tan ◽

Jung Eun Park ◽

JebaMercy Gnanasekaran ◽

Nikhil Gupta ◽

...

Keyword(s):

Lung Cancer ◽

Extracellular Vesicles ◽

Cancer Progression ◽

Membrane Trafficking ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Functional Clustering ◽

Signalling Molecules ◽

Proteomic Approach

Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that hypoxic tumours synthesize hypoxia-sensitive proteins for packing into EVs to modulate their microenvironment for cancer progression. In the current report, we employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia sensitive proteins in tumour-derived EVs protein. The results revealed that hypoxia stimulated cells to synthesize EVs proteins involved in enhancing tumour cell proliferation (NRSN2, WISP2, SPRX1, LCK), metastasis (GOLM1, STC1, MGAT5B), stemness (STC1, TMEM59), angiogenesis (ANGPTL4), and suppressing host immunity (CD70). In addition, functional clustering analyses revealed that tumour hypoxia was strongly associated with rapid synthesis and EV loading of lysosome-related hydrolases and membrane-trafficking proteins to enhance EVs secretion. Moreover, lung cancer-derived EVs were also enriched in signalling molecules capable of inducing epithelial-mesenchymal transition in recipient cancer cells to promote their migration and invasion. Together, these data indicate that lung-cancer-derived EVs can act as paracrine/autocrine mediators of tumorigenesis and metastasis in hypoxic microenvironments. Tumour EVs may, therefore, offer novel opportunities for useful biomarkers discovery and therapeutic targeting of different cancer types and at different stages according to microenvironmental conditions.

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The Role of Long Non-Coding RNA NNT-AS1 in Neoplastic Disease

Cancers ◽

10.3390/cancers12113086 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3086

Author(s):

Cong Zhou ◽

Shiwei Duan

Keyword(s):

Cancer Progression ◽

Cisplatin Resistance ◽

Malignant Tumors ◽

Human Cancer ◽

Neoplastic Disease ◽

Expression Levels ◽

Cancer Breast ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Studies have shown that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), play an important regulatory role in the occurrence and development of human cancer. Nicotinamide nucleotide transhydrogenase-antisense 1 (NNT-AS1) is a newly-discovered cytoplasmic lncRNA. Many studies have shown that it has abnormally-high expression levels in malignant tumors, but there are also a few studies that have reported low expression levels of NNT-AS1 in gastric cancer, breast cancer, and ovarian cancer. At present, the regulatory mechanism of NNT-AS1 as a miRNA sponge, which may be an important reason affecting tumor cell proliferation, invasion, metastasis, and apoptosis is being studied in-depth. In addition, NNT-AS1 has been found to be related to cisplatin resistance. In this review, we summarize the abnormal expression of NNT-AS1 in a variety of neoplastic diseases and its diagnostic and prognostic value, and we explain the mechanism by which NNT-AS1 regulates cancer progression by competing with miRNAs. In addition, we also reveal the correlation between NNT-AS1 and cisplatin resistance and the potential clinical applications of NNT-AS1.

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LncRNA DQ786243 contributes to proliferation and metastasis of colorectal cancer both in vitro and in vivo

Bioscience Reports ◽

10.1042/bsr20160048 ◽

2016 ◽

Vol 36 (3) ◽

Cited By ~ 16

Author(s):

Longci Sun ◽

Hanbing Xue ◽

Chunhui Jiang ◽

Hong Zhou ◽

Lei Gu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Cell Cycle Progression ◽

Migration And Invasion ◽

Cycle Progression ◽

Proliferation And Metastasis ◽

Non Coding Rnas ◽

Colorectal Cancer Progression

This article aims to find the key long non-coding RNAs (LncRNAs) associated with colorectal cancer (CRC) and to study its biological functions in colorectal cancer progression. Our study has shown that upregulated LncRNA DQ786243 can regulate cell proliferation, cell cycle progression, cell apoptosis, migration, and invasion in CRC cells. Xenograft experiments confirmed that the growth of xenograft tumors formed by CRC cells was suppressed after silencing LncRNA DQ786243 expression. In conclusion, our study suggests that LncRNA DQ786243 is an oncogene that promotes tumor progression and leads us to propose that LncRNAs may serve as key regulatory hubs in CRC progression.

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