scholarly journals Anti-tumor effect of HOTAIR–miR-613-SNAI2 axis through suppressing EMT and drug resistance in laryngeal squamous cell carcinoma

RSC Advances ◽  
2018 ◽  
Vol 8 (52) ◽  
pp. 29879-29889 ◽  
Author(s):  
Jing-chun Zhou ◽  
Jing-jing Zhang ◽  
Wei Ma ◽  
Wei Zhang ◽  
Zhao-yang Ke ◽  
...  

Laryngeal squamous cell carcinoma (LSCC) is the main pathological type of laryngeal cancer, which attacks the head and neck.

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Ruihua Fang ◽  
Yongjin Huang ◽  
Jinghua Xie ◽  
Jianzhong Zhang ◽  
Xiaobin Ji

Abstract Background Laryngeal squamous cell carcinoma (LSCC) is considered to be a common malignancy of the head and neck with poor prognosis for its late diagnosis, metastasis and recurrence. Growing evidence demonstrates that the dysregulation of miR-29c-3p (microRNA-29c-3p) plays an important role in various tumor processes. Our study investigates the expression of miR-29c-3p in LSCC and analyzes the correlation of its dysregulation with clinicopathologic parameters and prognosis. Methods The expression of hsa-miR-29c-3p in LSCC tissues and the adjacent normal laryngeal tissues was detected in 96 LSCC formalin-fixed paraffin-embedded tissues by quantitative real-time PCR (qRT-PCR). The SPSS statistical software package (17.0) was used to analyze the associations between miR-29c-3p expressions and various clinicopathological characteristics. The overall survival (OS) was analyzed by the Kaplan-Meier method and log-rank test, and we analyzed the independent factor of prognosis by Cox proportional hazard analysis. Results A downregulation of miR-29c-3p expression in LSCC was significantly correlated with smoking index, tumor size, tumor site, differentiation, T classification, TNM stage, and lymph node metastasis (P < 0.05), but there was no correlation with age and alcohol consumption (P > 0.05). In the multivariate survival analysis, low miR-29c-3p expression was associated with shorter overall survival (P < 0.05). Furthermore, miR-29c expression was an independent prognostic factor for laryngeal cancer patients. Conclusions MiR-29c-3p has different expression levels at different stages of tumor progression, suggesting that miR-29c-3p may be a promising biomarker for evaluating the progression of LSCC and the prognosis of patients with LSCC. MiR-29c-3p can also be a novel molecular target for anti-laryngeal cancer therapy.


Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770551 ◽  
Author(s):  
Mei Wang ◽  
Chunping Wu ◽  
Yu Guo ◽  
Xiaojuan Cao ◽  
Wenwei Zheng ◽  
...  

Most primarily cultured laryngeal squamous cell carcinoma cells are difficult to propagate in vitro and have a low survival rate. However, in our previous work to establish a laryngeal squamous cell carcinoma cell line, we found that laryngeal cancer-associated fibroblasts appeared to strongly inhibit the apoptosis of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In this study, we investigated whether paired laryngeal cancer-associated fibroblasts alone can effectively support the growth of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In all, 29 laryngeal squamous cell carcinoma specimens were collected and primarily cultured. The laryngeal squamous cell carcinoma cells were separated from cancer-associated fibroblasts by differential trypsinization and continuously subcultured. Morphological changes of the cultured laryngeal squamous cell carcinoma cells were observed. Immunocytofluorescence was used to authenticate the identity of the cancer-associated fibroblasts and laryngeal squamous cell carcinoma cells. Flow cytometry was used to quantify the proportion of apoptotic cells. Western blot was used to detect the protein levels of caspase-3. Enzyme-linked immunosorbent assay was used to detect the levels of chemokine (C-X-C motif) ligand 12, chemokine (C-X-C motif) ligand 7, hepatocyte growth factor, and fibroblast growth factor 1 in the supernatants of the laryngeal squamous cell carcinoma and control cells. AMD3100 (a chemokine (C-X-C motif) receptor 4 antagonist) and an anti–chemokine (C-X-C motif) ligand 7 antibody were used to block the tumor-supporting capacity of cancer-associated fibroblasts. Significant apoptotic changes were detected in the morphology of laryngeal squamous cell carcinoma cells detached from cancer-associated fibroblasts. The percentage of apoptotic laryngeal squamous cell carcinoma cells and the protein levels of caspase-3 increased gradually in subsequent subcultures. In contrast, no significant differences in the proliferation capacity of laryngeal squamous cell carcinoma cells cocultured with cancer-associated fibroblasts were detected during subculturing. High level of chemokine (C-X-C motif) ligand 12 was detected in the culture supernatant of cancer-associated fibroblasts. The tumor-supporting effect of cancer-associated fibroblasts was significantly inhibited by AMD3100. Our findings demonstrate that the paired laryngeal cancer-associated fibroblasts alone are sufficient to support the primary growth of laryngeal squamous cell carcinoma cells in vitro and that the chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 axis is one of the major contributors.


2003 ◽  
Vol 51 (4) ◽  
pp. 533-539 ◽  
Author(s):  
Jing Du ◽  
George G. Chen ◽  
Alexander C. Vlantis ◽  
Hu Xu ◽  
Raymond K.Y. Tsang ◽  
...  

The interaction between the HPV (human papilloma virus) 16 E7 and other cell growth factors, such as p53 and NFκB in laryngeal cancer is not clearly understood. The aim of this study was to examine the expression of these three proteins in tumor and non-tumor laryngeal tissues from patients with laryngeal squamous cell carcinoma. These three proteins were dominantly expressed in the nucleus and their levels were higher in the tumor tissue than in the non-tumor tissue, although the comparison between the tumor and non-tumor tissues of p53 staining did not reach significance. The intensity of the nuclear stain of E7 and p53 was stronger than that of p65, a subunit of NFκB. Correlation analysis revealed that there was a positive relationship between the level of HPV16 E7 and the expression of p65. The correlation between E7 and p53 was also significant, although to a lesser degree. The finding of nuclear localization of p65 suggests that NFκB is constantly activated in the laryngeal cancer cells, whereas the sequestration of p53 in the nucleus may represent a mutated form of p53, which is probably inactivated by HPV16 oncoproteins. In conclusion, this study suggests that the nuclear localization of NFκB and p53 may play a role in the development of human laryngeal squamous cell carcinoma infected with HPV16.


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.


Author(s):  
Jakob Pugi ◽  
Marc Levin ◽  
Michael Gupta

Abstract Background Head and neck cancer during pregnancy is uncommon. Specifically, laryngeal cancer in pregnancy has only been previously reported 10 times. HPV p16+ supraglottic cancer during pregnancy has never been described in the literature prior to this case report. This case is important to report to understand the most effective and safe diagnostic, treatment and follow-up options available for pregnant patients with laryngeal cancer. Case presentation This report describes a case of a 33-year-old patient who was 24 weeks pregnant presenting with dysphonia and odynophagia. After laryngeal biopsy and MRI she was diagnosed with T3N1M0, stage three p16+ squamous cell carcinoma of the supraglottis. After inter-disciplinary consultation as well as extensive patient discussion, an awake tracheostomy, PEG tube placement and then elective C-section at 28 weeks’ gestation was completed. This was followed by chemoradiotherapy. The patient has remained free from disease with a healthy child at four years post-treatment. Conclusion Supraglottic cancer during pregnancy is rare with only four previous cases reported in the literature. This case report elucidates the importance of including multiple specialities as well as patient preference in the decision-making process regarding treatment for patients with supraglottic cancer during pregnancy. Furthermore, diagnostic and treatment guidelines for pregnant patients with head and neck cancers should be established to promote the best possible oncological, obstetrical and neonatal care.


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