scholarly journals Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human Laryngeal Squamous Cell Carcinoma Cells

2018 ◽  
Vol 47 (4) ◽  
pp. 1696-1710 ◽  
Author(s):  
Yongyan Wu ◽  
Yuliang Zhang ◽  
Min Niu ◽  
Yong Shi ◽  
Hongliang Liu ◽  
...  

Background/Aims: CD133+CD44+ cancer stem cells previously isolated from laryngeal squamous cell carcinoma (LSCC) cell lines showed strong malignancy and tumorigenicity. However, the molecular mechanism underlying the enhanced malignancy remained unclear. Methods: Cell proliferation assay, spheroid-formation experiment, RNA sequencing (RNA-seq), miRNA-seq, bioinformatic analysis, quantitative real-time PCR, migration assay, invasion assay, and luciferase reporter assay were used to identify differentially expressed mRNAs, lncRNAs, circRNAs and miRNAs, construct transcription regulatory network, and investigate functional roles and mechanism of circRNA in CD133+CD44+ laryngeal cancer stem cells. Results: Differentially expressed genes in TDP cells were mainly enriched in the biological processes of cell differentiation, regulation of autophagy, negative regulation of cell death, regulation of cell growth, response to hypoxia, telomere maintenance, cellular response to gamma radiation, and regulation of apoptotic signaling, which are closely related to the malignant features of tumor cells. We constructed the regulatory network of differentially expressed circRNAs, miRNAs and mRNAs. qPCR findings for the expression of key genes in the network were consistent with the sequencing data. Moreover, our data revealed that circRNA hg19_circ_0005033 promotes proliferation, migration, invasion, and chemotherapy resistance of laryngeal cancer stem cells. Conclusions: This study provides potential biomarkers and targets for LSCC diagnosis and therapy, and provide important evidences for the heterogeneity of LSCC cells at the transcription level.

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12075
Author(s):  
Jinhua Ma ◽  
Xiaodong Hu ◽  
Baoqiang Dai ◽  
Qiang Wang ◽  
Hongqin Wang

In this study, a bioinformatics analysis is conducted to screen differentially expressed miRNAs and mRNAs in laryngeal squamous cell carcinoma (LSCC). Based on this information, we explored the possible roles of miRNAs in the pathogenesis of LSCC. The RNA-Seq data from 79 laryngeal cancer samples in the Gene Expression Omnibus (GEO) database were sorted. Differentially expressed miRNAs and mRNAs in LSCC are screened using the PERL programming language, and it was analysed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The miRNA-mRNA regulatory network of LSCC is constructed using Cytoscape software. Then, quantitative real-time PCR (QRT- PCR), Cell Counting Kit-8 (CCK8) and flow cytometry analysis we are used to further validate key miRNAs. We identified 99 differentially expressed miRNAs and 2,758 differentially expressed mRNAs in LSCC tissues from the GEO database. Four more important miRNAs displaying a high degree of connectivity are selected, these results suggest that they play an important role in the pathogenesis of LSCC. As shown in the present study, we identified specific miRNA-mRNA networks associated with the occurrence and development of LSCC through bioinformatics analysis. We found a miRNA molecule closely related to LSCC based on miRNA-mRNA network: miR-140-3p was down-regulated in LSCC. In addition, the potential antitumor effect of miR-140-3p in LSCC was verified in the experiment, and it was proved that overexpression of miR-140-3p could inhibit the proliferation of LSCC cells and promote cell apoptosis, suggesting that miR-140-3p may be a potential tumor marker in LSCC.


Author(s):  
Meriç Bilgiç Küçükgüven ◽  
Betül Çelebi-Saltik

: Head and Neck Squamous Cell Carcinoma (HNSCC) is categorized as the sixth most common cancer worldwide, with an incidence of more than 830,000 cases per year and a mortality rate of 50%. Tobacco use, alcohol consumption, and Human Papillomavirus infection are the prominent risks for HNSCC. Despite significant developments in the treatment of HNSCC, a high rate of recurrences makes the clinical situation worse and results in poor survival rates. Recent perspectives demonstrate that whereas epithelial transformation plays a crucial role in cancer development, tumor surrounding microenvironment takes part in progression of cancer as well. Cancer Stem Cells (CSCs), which harbor unlimited self-renewal capacity, have a crucial role in the growth of HNSCC and this cell population is responsible for tumor recurrence unless eliminated by targeted therapy. CSCs are not only a promising target for tumor therapy, but also a crucial biomarker to determine the patients at high risk for undetermined results and disease development. Just as the bone marrow which is the niche of hematopoietic and mesenchymal stem cells, is important for stem cells maintenance. Similarly, the concept of microenvironment is also important for the maintenance of CSCs. Apart from the cell-cell interactions, there are many parameters in the cancer microenvironment that affect the development of cancer, such as extracellular regulation, vascularization, microbial flora, pH and oxygenation. The purpose of this review is to introduce HNSCC, explain the role of CSCs and their microenvironment and refer to the conventional and novel targeted therapy for HNSCC and CSCs.


Author(s):  
Zhigeng Zou ◽  
Wei Zheng ◽  
Hongjun Fan ◽  
Guodong Deng ◽  
Shih-Hsin Lu ◽  
...  

Abstract Background Cancer stem cells (CSCs) are related to the patient’s prognosis, recurrence and therapy resistance in oesophageal squamous cell carcinoma (ESCC). Although increasing evidence suggests that aspirin (acetylsalicylic acid, ASA) could lower the incidence and improve the prognosis of ESCC, the mechanism(s) remains to be fully understood. Methods We investigated the role of ASA in chemotherapy/chemoprevention in human ESCC cell lines and an N-nitrosomethylbenzylamine-induced rat ESCC carcinogenesis model. The effects of combined treatment with ASA/cisplatin on ESCC cell lines were examined in vitro and in vivo. Sphere-forming cells enriched with putative CSCs (pCSCs) were used to investigate the effect of ASA in CSCs. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed to determine the alterations in chromatin accessibility caused by ASA in ESCC cells. Results ASA inhibits the CSC properties and enhances cisplatin treatment in human ESCC cells. ATAC-seq indicates that ASA treatment results in remarkable epigenetic alterations on chromatin in ESCC cells, especially their pCSCs, through the modification of histone acetylation levels. The epigenetic changes activate Bim expression and promote cell death in CSCs of ESCC. Furthermore, ASA prevents the carcinogenesis of NMBzA-induced ESCC in the rat model. Conclusions ASA could be a potential chemotherapeutic adjuvant and chemopreventive drug for ESCC treatment.


2015 ◽  
Vol 47 (4) ◽  
pp. 1249-1256 ◽  
Author(s):  
KAZUYA YATA ◽  
LEVENT BEKIR BEDER ◽  
SHUNJI TAMAGAWA ◽  
MUNEKI HOTOMI ◽  
YOSHIHIKO HIROHASHI ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhisen Shen ◽  
Chongchang Zhou ◽  
Jinyun Li ◽  
Dong Ye ◽  
Hongxia Deng ◽  
...  

The purpose of this study was to evaluate the contribution ofSHISA3promoter methylation to laryngeal squamous cell carcinoma (LSCC).SHISA3promoter methylation status and expression were determined using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) in 93 paired LSCC and adjacent normal tissues, respectively. Furthermore, the regulatory function of theSHISA3promoter fragment was analyzed using a luciferase reporter assay. The results reveal that there is a significant increase inSHISA3methylation in LSCC tissues compared with corresponding nontumor tissuesP=4.58E-12. The qRT-PCR results show a significant association betweenSHISA3methylation and expression in LSCCP=1.67E-03. In addition, the area under the receiver operating characteristic curve was 0.91. Consequently, a log-rank test and multivariate Cox analysis suggest thatSHISA3promoter hypermethylation is a predictor of poor overall survival for LSCC (log-rankP= 0.024; HR = 2.71; 95% CI = 1.024–7.177;P= 0.047). The results indicate thatSHISA3promoter hypermethylation might increase the risk of LSCC through regulation of gene expression and is a potential diagnostic and prognostic biomarker for LSCC.


Tumor Biology ◽  
2014 ◽  
Vol 35 (11) ◽  
pp. 11605-11612 ◽  
Author(s):  
Shunli Liu ◽  
Zhenyu Gong ◽  
Mingrui Chen ◽  
Benli Liu ◽  
Donghui Bian ◽  
...  

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