scholarly journals Deregulation of Hexokinase II Is Associated with Glycolysis, Autophagy, and the Epithelial-Mesenchymal Transition in Tongue Squamous Cell Carcinoma under Hypoxia

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Guanhui Chen ◽  
Yadong Zhang ◽  
Jianfeng Liang ◽  
Wenqing Li ◽  
Yue Zhu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Tongue Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Control Group ◽  
Mesenchymal Transition

The glycolytic enzyme Hexokinase (HKII) participates in tumor glycolysis and the progression of various cancers, but its clinicopathological effect on the progression of tongue squamous cell carcinoma (TSCC) and its role in glycolysis, autophagy, and the epithelial-mesenchymal transition of TSCC in a hypoxic microenvironment remain unknown. Our results showed that HKII expression was dramatically increased in TSCC tissues and that its upregulation was significantly associated with the presence of pathological differentiation, lymph node metastasis, and clinical stage. The level of autophagy-specific protein LC3, EMT-related proteins, and the migration and invasion capabilities of TSCC cells all increased under hypoxia. Moreover, hypoxia increased the glucose consumption and lactate production of TSCC cells, and we demonstrated that the expression of the glycolytic key gene HKII was significantly higher than in that of the control group. Notably, the downregulation of HKII resulted in a significant decrease of TSCC cell glucose consumption lactate production and autophagic activity during hypoxia. HKII knockdown blocked the migratory and invasive capacity of TSCC cells and we specifically determined that the EMT ability decreased. Therefore, our findings revealed that the upregulation of HKII enhanced glycolysis and increased autophagy and the epithelial-mesenchymal transition of tongue squamous cell carcinoma under hypoxia.

scholarly journals The Role of MicroRNAs in Recurrence and Metastasis of Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 395 ◽  
Author(s):  
Chris Yang ◽  
Wafik Sedhom ◽  
John Song ◽  
Shi-Long Lu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Neck Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Mesenchymal Transition ◽  
Underlying Mechanisms

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.

scholarly journals MicroRNA-138 suppresses epithelial–mesenchymal transition in squamous cell carcinoma cell lines

2011 ◽  
Vol 440 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Xiqiang Liu ◽  
Cheng Wang ◽  
Zujian Chen ◽  
Yi Jin ◽  
Yun Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Direct Targeting

Down-regulation of miR-138 (microRNA-138) has been frequently observed in various cancers, including HNSCC (head and neck squamous cell carcinoma). Our previous studies suggest that down-regulation of miR-138 is associated with mesenchymal-like cell morphology and enhanced cell migration and invasion. In the present study, we demonstrated that these miR-138-induced changes were accompanied by marked reduction in E-cad (E-cadherin) expression and enhanced Vim (vimentin) expression, characteristics of EMT (epithelial–mesenchymal transition). On the basis of a combined experimental and bioinformatics analysis, we identified a number of miR-138 target genes that are associated with EMT, including VIM, ZEB2 (zinc finger E-box-binding homeobox 2) and EZH2 (enhancer of zeste homologue 2). Direct targeting of miR-138 to specific sequences located in the mRNAs of the VIM, ZEB2 and EZH2 genes was confirmed using luciferase reporter gene assays. Our functional analyses (knock-in and knock-down) demonstrated that miR-138 regulates the EMT via three distinct pathways: (i) direct targeting of VIM mRNA and controlling the expression of VIM at a post-transcriptional level, (ii) targeting the transcriptional repressors (ZEB2) which in turn regulating the transcription activity of the E-cad gene, and (iii) targeting the epigenetic regulator EZH2 which in turn modulates its gene silencing effects on the downstream genes including E-cad. These results, together with our previously observed miR-138 effects on cell migration and invasion through targeting RhoC (Rho-related GTP-binding protein C) and ROCK2 (Rho-associated, coiled-coil-containing protein kinase 2) concurrently, suggest that miR-138 is a multi-functional molecular regulator and plays major roles in EMT and in HNSCC progression.

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