scholarly journals NFIB-Mediated lncRNA PVT1 Aggravates Laryngeal Squamous Cell Carcinoma Progression via the miR-1301-3p/MBNL1 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Tian Tang ◽  
Feng Zeng

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of head and neck cancers. In the past decades, although the therapy strategies of LSCC have made considerable improvement, the terrible outcomes of LSCC still bring an enormous burden to the world health care system. Novel therapeutic targets for LSCC are urgently needed. lncRNAs exert important roles in various biological progressions, including LSCC. Here, we aimed to investigate the function of lncRNA PVT1 in LSCC progression and its underlying molecular mechanisms. By conducting multiple experiments, our results showed that lncRNA PVT1 was upregulated in LSCC cell lines and regulated LSCC cell proliferation, apoptosis, and its cell susceptibility to natural killer (NK) cells. Moreover, it was found that lncRNA PVT1 promotes MBNL1 expression to regulate LSCC cellular progression through sponging miR-1301-3p. Our study might provide novel targets for LSCC basic research or clinical management.

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jiechao Yang ◽  
Liang Zhou ◽  
Yanping Zhang ◽  
Juan Zheng ◽  
Jian Zhou ◽  
...  

Cancer bioinformatics has been used to screen possible key cancer genes and pathways. Here, through bioinformatics analysis, we found that high expression of diaphanous related formin 1 (DIAPH1) was associated with poor overall survival in head and neck squamous cell carcinoma and laryngeal squamous cell carcinoma (LSCC). The effect of DIAPH1 in LSCC has not been previously investigated. Therefore, we evaluated the expression, function, and molecular mechanisms of DIAPH1 in LSCC. Immunohistochemistry and western blot analysis confirmed the significant upregulation of DIAPH1 in LSCC. We used DIAPH1 RNA interference to construct two DIAPH1-knockdown LSCC cell lines, AMC-HN-8 and FD-LSC-1, and validated the knockdown efficiency. Flow cytometry data showed that DIAPH1 inhibited apoptosis. Further, western blot analysis revealed that DIAPH1 knockdown increased the protein levels of ATR, p-p53, Bax, and cleaved caspase-3, -8, and -9. Thus, DIAPH1 is upregulated in LSCC and may act as an oncogene by inhibiting apoptosis through the ATR/p53/caspase-3 pathway in LSCC cells.


2019 ◽  
Vol 133 (9) ◽  
pp. 1053-1066 ◽  
Author(s):  
Linli Tian ◽  
Jing Cao ◽  
Hui Jiao ◽  
Jiarui Zhang ◽  
Xiuxia Ren ◽  
...  

Abstract Background: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with laryngeal squamous cell carcinoma (LSCC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for LSCC from the aspect of circRNA–microRNA (miRNA)–mRNA interaction. Methods: We investigated the expression of circRNAs in three paired LSCC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between LSCC tissues and non-cancerous matched tissues, including 527 up-regulated circRNAs and 414 down-regulated circRNAs. We focused on hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2. Results: circRASSF2 was found to be significantly up-regulated in LSCC tissues and LSCC cell lines compared with paired adjacent non-tumorous tissues and normal cells. Moreover, knockdown of circRASSF2 significantly inhibited cell proliferation and migration in vitro, which was blocked by miR-302b-3p inhibitor. Bioinformatics analysis predicted that there is a circRASSF2/miR-302b-3p/ insulin-like growth factor 1 receptor (IGF-1R) axis in LSCC progression. Dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-302b-3p, and IGF-1R. Western blot verified that inhibition of circRASSF2 decreased IGF-1R expression. Furthermore, silencing circRASSF2 suppressed LSCC growth in vivo. Importantly, we demonstrated that circRASSF2 was up-regulated in serum exosomes from LSCC patients. Altogether, silencing circRASSF2 suppresses progression of LSCC by interacting with miR-302b-3p and decreasing inhibiting IGF-1R expression. Conclusion: In conclusion, these data suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via an miR-302b-3p/IGF-1R axis.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Luo ◽  
Jianhui Wu ◽  
Zenghong Li ◽  
Hao Qin ◽  
Bin Wang ◽  
...  

MicroRNAs (miRNAs) are small noncoding RNA molecules which are involved in tumorigenesis and development. To investigate their role in primary laryngeal squamous cell carcinoma (LSCC), miRNA GeneChips were used to screen the differentially expressed miRNA, and then validated by real-time quantitative PCR in LSCC samples, we found that miR-375 was frequently downregulated in primary LSCC tissues. The tumor-suppressive effect of miR-375 was determined by in vitro assays; through gain-of-function studies we demonstrated that miR-375 can inhibit LSCC cell (SNU-48 and SNU-899) proliferation, motility, and invasion, and promote their apoptosis. In addition, bioinformatics tools TargetScan, PicTar, and Miranda were used to investigate the potential target of miR-375; bioinformatics analysis and dual-luciferase reporter assay indicated that IGF1R was a novel direct target of miR-375. Ectopic transfection of miR-375 led to a significant reduction in IGF1R and its downstream signaling molecule AKT at both the mRNA and protein levels in LSCC cells. Our results suggested that downregulation of miR-375 is one of the molecular mechanisms for the development and progression of LSCC by directly targeting IGF1R and affecting its downstream AKT signaling pathways. Furthermore, miR-375 and IGF1R may serve as a novel therapeutic target for LSCC.


2021 ◽  
Author(s):  
Weixing Liu ◽  
Pei Li ◽  
Yue Liu ◽  
Zhiyuan Wang ◽  
Jiamin Liu ◽  
...  

Abstract Background: Increasing studies have demonstrated that immune associated lncRNAs (IALs) take an important part in the occurrence and development of multiple cancers. However, the prognosis value of IALs in laryngeal squamous cell carcinoma (LSCC) remains unexplored. This study aimed to evaluate the importance of IALs in LSCC. Methods: RNA sequencing data profiles of LSCC and clinical information of patients were obtained from TCGA dataset. Correlation analysis was performed to screen IALs. Then, a IALs based prognostic signature was constructed through univariate and multivariate Cox regression. The uncover molecular mechanisms of these selected IALs were explored by the bioinformatics analyses.Results: a total of seven differentially expressed survival-associated IALs were found in LSCC patients. a six IALs (LINC02154, SNHG12, CHKB-DT, AL158166.1, AC027307.2 and AL121899.1) based prognostic signature was established, which was a reliable tool to predict the prognosis of LSCC. The area under the curve (AUC) were 0.817 (one-year), 0.847 (three-year) and 0.895 (five-year). Further analysis, there were different infiltration of immune cells between low-risk and high-risk group patients. Additionally, a lncRNA-miRNA-mRNA regulatory network basted on six IALs, 75 miRNAs, and 156 differentially expressed mRNAs was constructed.Conclusions: IALs may play critical role in the occurrence and progression of LSCC, and the IALs based prognostic signature can predict the overall survival rate of LSCC.


2021 ◽  
Vol 9 (A) ◽  
pp. 1168-1173
Author(s):  
Wala’a Ahmad Al-Sayed Ashmawy ◽  
Ahmed Mahmoud Abd-Elaziz ◽  
Amira Mohamed Bassam ◽  
Heba Abdelmonem Ibrahim

BACKGROUND: IMP3 is an RNA binding protein, which is strongly expressed in malignant tumors, promoting tumor cell proliferation. AIM: The aim of the study was to evaluate the expression of IMP3 in laryngeal squamous cell carcinoma (SCC) and to correlate the expression of IMP3 with available clinicopathological data. METHODS: Sixty one total laryngectomy and laryngoscopic biopsies; collected from the Pathology Department, Faculty of Medicine, Cairo University. Two slides were prepared from each paraffin embedded tumor block, one slide for Hematoxylin and Eosin staining, and the other for immunohistochemical staining by IMP3 polyclonal antibody. RESULTS: Thirty-seven cases (60.7%) showed positive IMP3 expression, and a statistically significant correlation was found between IMP3 expressions in normal, dysplastic epithelium/in situ component, and the invasive malignant tumor tissue. Correlations between IMP3 expression and other available clinicopathological data were all non-significant. CONCLUSION: This study suggests that IMP3 might play a role in laryngeal SCC carcinogenesis and progression process from normal to dysplastic to malignant epithelium, and thus IMP3 might be targeted by gene therapy.


2020 ◽  
Vol 10 ◽  
Author(s):  
Xin Li ◽  
Ping Wu ◽  
Yaoyun Tang ◽  
Yuhua Fan ◽  
Yalan Liu ◽  
...  

Laryngeal squamous cell carcinoma (LSCC) arises from the squamous epithelium of the larynx and is associated with a high incidence of cervical lymph node metastasis. MicroRNAs (miRNAs) play a crucial role in the epigenetic regulation of cellular biological processes, including cancer metastasis. However, the molecular mechanisms of specific miRNAs responsible for LSCC metastasis and their clinical significance have yet to be fully elucidated. In this study, LSCC cohort datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were downloaded and examined by comprehensive bioinformatics analysis, which revealed that upregulation of mRNA SERPINE1 and downregulation of miR-181c-5p were associated with unfavorable overall survival. Our analysis showed that SERPINE1 expression negatively correlated with the expression level of miR-181c-5p in our LSCC patient samples. Silencing of miR-181c-5p expression promoted cell migration and invasion in cell lines, whereas the overexpression of miR-181c-5p suppressed cell migration and epithelial-to-mesenchymal transition (EMT) through the downregulation of SERPINE1. Further analysis showed that the enhancement effect on EMT and metastasis induced by silencing miR-181c-5p could be rescued through knockdown of SERPINE1 expression in vitro. Collectively, our findings indicated that miR-181c-5p acted as an EMT suppressor miRNA by downregulation of SERPINE1 in LSCC and offers novel strategies for the prevention of metastasis in LSCC.


OBM Genetics ◽  
2020 ◽  
Vol 05 (02) ◽  
pp. 1-1
Author(s):  
Jessica Lin ◽  
◽  
Valentina L Kouznetsova ◽  
Igor F Tsigelny ◽  
◽  
...  

Feline cancers have not been studied as extensively as canine cancers, though they may offer similar advantages, with cats being immunocompetent animals subject to similar conditions as their human counterparts. The most common feline cancers include lymphoma, squamous cell carcinoma, sarcoma, and mammary tumors, though mast cell tumors were also investigated in this review. As the pathogenesis of many feline cancers remains unclear, this study seeks to elucidate some molecular mechanisms behind feline cancers. Feline lymphoma has been commonly associated with feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV), though in recent years it has appeared more as lymphoma of the gastrointestinal tract. Chromosomal alterations (translocations) due to the virus-associated lymphoma, as well as aberrant gene expression (such as in COX-2 and MDR1) have been identified in the past. While feline lymphoma may be divided into many subtypes, feline sarcoma may be divided into two broad classifications of feline injection site associated (FISS) sarcoma and spontaneous sarcoma, with FISS being a potential model for inflammation leading to tumorigenesis in humans. Previous studies have found multiple chromosomal alterations (including aneuploidy and chromosomal translocations), as well as aberrations in gene expression in feline sarcoma. In the past, oral squamous cell carcinoma has been proposed as a model for human head and neck cancer, and mammary tumors have been proposed as a model for human breast cancers due to similar prognosis and phenotype, as well as higher rate of occurrence in cats than in humans. Mutations have been identified in genes such as TP53, ERBB2, and TWIST1 in feline mammary tumors. c-KIT mutations were commonly located in feline mast cell tumors, though these findings were not particularly significant in terms of correlation to other prognostic indicators. This review seeks to elucidate pathways and treatments for feline cancers for the field of comparative genomics and oncology.


2013 ◽  
Vol 127 (12) ◽  
pp. 1194-1202 ◽  
Author(s):  
Z Shen ◽  
G Zhan ◽  
H Deng ◽  
Y Ren ◽  
D Ye ◽  
...  

AbstractObjective:This study investigated the expression and functional effects, and related molecular mechanisms, of microRNA-519a in laryngeal squamous cell carcinoma.Methods:MicroRNA-519a and HuR messenger RNA in laryngeal squamous cell carcinoma were measured using reverse transcription polymerase chain reaction. MicroRNA-519a effects on the growth of human epithelial type 2 cells were tested using an MTT assay. The influence of microRNA-519a on the expression levels of HuR and other related genes in protein was tested by Western blotting. Cell cycle analyses were performed using flow cytometry. Associations between expression levels and patients' clinical parameters were analysed with Pearson correlation analysis.Results:Expression of microRNA-519a in laryngeal squamous cell carcinoma tissues was significantly lower than in adjacent non-cancerous tissues. The expression of microRNA-519a was negatively associated with histological differentiation, tumour–node–metastasis stage, lymphatic metastasis and disease-free survival time. After increasing the level of microRNA-519a in laryngeal squamous cell carcinoma human epithelial type 2 cells, cell growth was inhibited and cell cycle was arrested in the G2/M phase. MicroRNA-519a down-regulated HuR gene expression in protein levels without affecting messenger RNA levels.Conclusion:MicroRNA-519a may function as a tumour suppressor by inhibiting HuR expression, and may serve as a therapeutic target for laryngeal squamous cell carcinoma.


1988 ◽  
Vol 50 (3) ◽  
pp. 466-471 ◽  
Author(s):  
Kazuo ASO ◽  
Shigeo KONDO ◽  
Noriaki SATO ◽  
Shin-ichi ANZAI ◽  
Jinko OBATA ◽  
...  

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