scholarly journals Hypoxia-induced MFAP5 Promotes Tumor Migration and Invasion via AKT Pathway in Head and Neck Squamous Cell Carcinoma

2020 ◽  
Vol 11 (6) ◽  
pp. 1596-1605
Author(s):  
Qiaoshi Xu ◽  
Hanyue Chang ◽  
Xuerui Tian ◽  
Chao Lou ◽  
Hailong Ma ◽  
...  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiang Wu ◽  
Jin Li ◽  
Tingyuan Yan ◽  
Xueping Ke ◽  
Xin Li ◽  
...  

Abstract Background The homeobox gene Homeobox B7 (HOXB7) is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, migration and invasion. However, its expression pattern and oncogenic role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we aimed to explore the expression pattern of HOXB7, its clinical significance as well as functional roles in HNSCC. Methods HOXB7 mRNA expression in HNSCC was determined by data mining and analyses from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The protein abundance of HOXB7 was measured by immunohistochemistry in 119 primary HNSCC samples and associations between its expression and clinicopathological parameters and patient survival were evaluated. The pro-tumorigenic roles of HOXB7 in HNSCC were further delineated in vitro by loss-of-function assay. And a xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Connectivity Map (CMap) analysis was performed to identify bioactive small molecules which might be potential inhibitors for HOXB7. Results Bioinformatics analyses showed that HOXB7 mRNA was significantly overexpressed in 8 independent HNSCC datasets from TCGA and GEO databases. HOXB7 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with high pathological grade, advanced clinical stage, cervical node metastasis (P = 0.0195, 0.0152, 0.0300) and reduced overall and disease-free survival (P = 0.0014, 0.0007). Univariate and multivariate Cox regression analyses further revealed HOXB7 as an independent prognostic factor for patients’ overall survival. Moreover, HOXB7 knockdown significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in HNSCC cells, and resulted in compromised tumour growth in vivo. Furthermore, CMap (Connectivity map) analysis has identified three potential bioactive small molecule inhibitors (NU-1025, thiamine, vinburnine) for HOXB7 targeted therapy in HNSCC. Conclusions Our findings revealed that overexpression of HOXB7 was associates with tumour aggressiveness and unfavourable prognosis by serving a novel prognostic biomarker in HNSCC. Moreover, HOXB7 might be involved in the development and progression of HNSCC as an oncogene, and thereby might be a potential therapeutic target for HNSCC.


Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 395 ◽  
Author(s):  
Chris Yang ◽  
Wafik Sedhom ◽  
John Song ◽  
Shi-Long Lu

Head and neck squamous cell carcinoma (HNSCC) affects 650,000 people worldwide and has a dismal 50% 5-year survival rate. Recurrence and metastasis are believed the two most important factors causing this high mortality. Understanding the biological process and the underlying mechanisms of recurrence and metastasis is critical to develop novel and effective treatment, which is expected to improve patients’ survival of HNSCC. MicroRNAs are small, non-coding nucleotides that regulate gene expression at the transcriptional and post-transcriptional level. Oncogenic and tumor-suppressive microRNAs have shown to regulate nearly every step of recurrence and metastasis, ranging from migration and invasion, epithelial-mesenchymal transition (EMT), anoikis, to gain of cancer stem cell property. This review encompasses an overview of microRNAs involved in these processes. The recent advances of utilizing microRNA as biomarkers and targets for treatment, particularly on controlling recurrence and metastasis are also reviewed.


2013 ◽  
Vol 42 (10) ◽  
pp. 793-798 ◽  
Author(s):  
Aline Corrêa Abrahão ◽  
Fernanda Salgueiredo Giudice ◽  
Felipe Fornias Sperandio ◽  
Décio dos Santos Pinto Junior

2021 ◽  
Vol 11 ◽  
Author(s):  
Tingting Zhang ◽  
Xueqin Zhu ◽  
Qiang Sun ◽  
Xing Qin ◽  
Zhen Zhang ◽  
...  

Constituents of tobacco that can cause DNA adduct formation and oxidative stress are implicated in the development of head and neck squamous cell carcinoma (HNSCC). However, there are few studies on the mechanism(s) that underlie tobacco-associated HNSCC. Here, we used a model in which tumors were induced in rats using 4-nitroquinoline 1-oxide (4NQO), which mimicked tobacco-related HNSCC, and analyzed the expression profiles of microRNAs and mRNAs. Our results indicated that 57 miRNAs and 474 mRNA/EST transcripts exhibited differential expression profiles between tumor and normal tongue tissues. In tumor tissue, the expression levels of rno-miR-30 family members (rno-miR-30a, rno-miR-30a-3p, rno-miR-30b-5p, rno-miR-30c, rno-miR-30d, rno-miR-30e and rno-miR-30e-3p) were only 8% to 37% of those in the control group. The GO terms enrichment analysis of the differentially expressed miRNAs indicated that oxidation reduction was the most enriched process. Low expression of miR-30 family members in human HNSCC cell lines and tissues was validated by qPCR. The results revealed that the expression of miR-30b-5p and miR-30e-5p was significantly decreased in the TCGA HNSCC dataset and validation datasets, and this decrease in expression further distinguishes HNSCC associated with tobacco use from other subtypes of HNSCC. CCK8, colony formation, transwell migration and HNSCC xenograft tumor assays indicated that miR-30b-5p or miR-30e-5p inhibited proliferation, migration and invasion in vitro, and miR-30b-5p suppressed tumor growth in vivo. Moreover, we uncovered that KRAS might be the potential target gene of miR-30e-5p or miR-30b-5p. Thus, our data clearly showed that decreased expression of miR-30e-5p or miR-30b-5p may play a crucial role in cancer development, especially that of tobacco-induced HNSCC, and may be a novel candidate biomarker and target for this HNSCC subtype.


2012 ◽  
Vol 75 (6) ◽  
pp. 1803-1815 ◽  
Author(s):  
Koji Katada ◽  
Takeshi Tomonaga ◽  
Mamoru Satoh ◽  
Kazuyuki Matsushita ◽  
Yurie Tonoike ◽  
...  

2011 ◽  
Vol 121 (11) ◽  
pp. 2359-2365 ◽  
Author(s):  
Joseph A. Knowles ◽  
Blake Golden ◽  
Li Yan ◽  
William R. Carroll ◽  
Emily E. Helman ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document