scholarly journals Regulation of Oral Squamous Cell Carcinoma Proliferation Through Crosstalk Between SMAD7 and CYLD

2016 ◽  
Vol 38 (3) ◽  
pp. 1209-1217 ◽  
Author(s):  
Wei-Li Ge ◽  
Jun-Feng Xu ◽  
Jun Hu

Background/Aims: SMAD7 is a key inhibitor of transforming growth factor β (TGFβ) receptor signaling, which regulates the alteration of cancer cell invasiveness through epithelial-mesenchymal cell conversion. Dysfunction of protein ubiquitination plays a critical role in carcinogenesis, whereas the involvement a deubiquitinating enzyme, cylindromatosis gene (CYLD), in the tumor invasion of oral squamous cell carcinoma (OSCC) is unknown. Methods: Here, we studied the role of CYLD in regulation of OSCC cell invasion, using clinic specimens and cell lines. We modified SMAD7 levels in OSCC cells, and examined its effects on CYLD mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified CYLD levels in OSCC cells, and examined its effects on SMAD7 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in CYLD and/or SMAD7-modified OSCC cells in a transwell cell invasion assay. Results: We found that the levels of CYLD and SMAD7 were significantly decreased in OSCC specimens, compared to the paired normal tissue. Metastatic OSCC appeared to contained lower levels of CYLD and SMAD7. Moreover, CYLD and SMAD7 levels strongly correlated in OSCC specimens. Low CYLD levels were associated with poor patients' survival. Moreover, SMAD did not regulate CYLD, but CYLD regulated the levels of SMAD7 in OSCC cells. Furthermore, CYLD overexpression inhibited SMAD7-mediated cell invasion, while CYLD depletion increased SMAD7-mediated cell invasion in OSCC cells. Conclusion: Suppression of CYLD in OSCC cells may promote SMAD7-mediated cancer invasion. Thus, CYLD appears to be an intriguing therapeutic target to prevent OSCC metastases.

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Yi Liu ◽  
Ronghua Li ◽  
Gang Ren

Abstract Aims: Oral squamous cell carcinoma (OSCC) is a common oral cancer; however, current therapeutic approaches still show limited efficacy. Our research aims to explore effective biomarkers related to OSCC. Main methods: Gene expression profiles of paired OSCC tumor and paracancerous samples from The Cancer Genome Atlas (TCGA) were analyzed. mRNA and protein levels of KRT84 in OSCC cell line HSC-3 were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. KRT84 protein levels in OSCC tumor samples of different stages were determined by immunohistochemistry. Overall survival (OS) of OSCC samples was evaluated and association of multiple factors with OS was assessed. Key findings: Compared with paracancerous samples, 4642 DEGs were identified in OSCC tumor samples. Among them, KRT84 expression level in OSCC tumor tissues was obviously decreased, which was validated in HSC-3 cells. KRT84 expression level showed decreasing tendency with the increase of tumor grade and stage. Patients with low KRT84 expression level had inferior OS independently of multiple factors. Besides, antigen processing and presentation pathway were significantly activated in OSCC samples with high KRT84 expression. Elevated KRT84 mRNA as well as protein levels were confirmed by RT-qPCR and Western blot in OSCC and normal cell lines, and immunohistochemistry in OSCC tumor and paracancerous tissues. Significance: Our study suggests KRT84 as a tumor suppressor and good prognostic indicator for OSCC, which might be significant for OSCC diagnosis and treatment.


2013 ◽  
Vol 36 (2) ◽  
pp. 87 ◽  
Author(s):  
Feng Wang ◽  
Yu Qi ◽  
Xin Li ◽  
Wei He ◽  
Qing-Xia Fan ◽  
...  

Purpose: The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) has been shown to act as an anti-tumor agent; however, the effect and mechanism of TSA on the invasion of esophageal squamous cell carcinoma (ESCC) remains unknown. Methods: To determine whether TSA suppresses the invasiveness of ESCC cell via HDAC2, the expression of HDAC2 in ESCC tissues and adjacent non-tumor tissues were compared using Western blot and immunohistochemistry. Cells were transfected with HDAC2 siRNAs and non-targeting control siRNA using Lipofectamine TM 2000. Cell invasion was investigated using a transwell assay. The protein levels of matrix metalloproteinase-2/9 (MMP-2/9) were examined by Western blot analysis. Results: Expression of HDAC2 was significantly higher in ESCC than in adjacent non-tumor tissues. Additionally, the in vitro invasion assay found that both downregulation of HDAC2 expression and TSA treatment inhibited ESCC cell invasion by approximately 75%. Also, an MMP2/9-specific inhibitor sharply suppressed ESCC cell invasion. Furthermore, both downregulation of HDAC2 and treatment with TSA decreased MMP-2 and MMP-9 protein levels in ESCC cells. Conclusions: These results suggest that the inhibitory effect of TSA on cancer invasion is mediated through the suppression of HDAC2 expression, and that the reduction of MMP-2 and MMP-9 expression induced by HDAC2 may be involved in the anti-invasive effect of TSA.


2020 ◽  
Vol 6 (6) ◽  
pp. 618-625
Author(s):  
Kary Y.F. Tsai ◽  
Kelsey M. Hirschi Budge ◽  
Anthony P. Lepre ◽  
Michael S. Rhees ◽  
Janet Ajdaharian ◽  
...  

2019 ◽  
Vol 8 (11) ◽  
pp. 1958 ◽  
Author(s):  
Ildikó Judit Márton ◽  
József Horváth ◽  
Péter Lábiscsák ◽  
Bernadett Márkus ◽  
Balázs Dezső ◽  
...  

Salivary IL-6 mRNA was previously identified as a promising biomarker of oral squamous cell carcinoma (OSCC). We performed a multi-center investigation covering all geographic areas of Hungary. Saliva from 95 patients with OSCC and 80 controls, all Caucasian, were collected together with demographic and clinicopathological data. Salivary IL-6 mRNA was quantified by real-time quantitative PCR. Salivary IL-6 protein concentration was measured by enzyme-linked immune-sorbent assay. IL-6 protein expression in tumor samples was investigated by immunohistochemistry. Normalized salivary IL-6 mRNA expression values were significantly higher (p < 0.001) in patients with OSCC (mean ± SE: 3.301 ± 0.885) vs. controls (mean ± SE: 0.037 ± 0.012). Differences remained significant regardless of tumor stage and grade. AUC of the ROC curve was 0.9379 (p < 0.001; 95% confidence interval: 0.8973–0.9795; sensitivity: 0.945; specificity: 0.819). Salivary IL-6 protein levels were significantly higher (p < 0.001) in patients (mean ± SE: 70.98 ± 14.06 pg/mL), than in controls (mean ± SE: 12.45 ± 3.29). Specificity and sensitivity of IL-6 protein were less favorable than that of IL-6 mRNA. Salivary IL-6 mRNA expression was significantly associated with age and dental status. IL-6 manifestation was detected in tumor cells and tumor-infiltrating leukocytes, suggesting the presence of a paracrine loop of stimulation. Salivary IL-6 mRNA is one of the best performing and clinically relevant biomarkers of OSCC.


2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Fei Le ◽  
Yangqian Ou ◽  
Ping Luo ◽  
Xiaoming Zhong

Abstract Background Oral squamous cell carcinoma (OSCC) at early stages can be misdiagnosed as an oral ulcer (OU) due to similar symptoms, such as chronic and indurated ulcer. LncRNA NCK1-AS1 has been characterized as a key player in cervical cancer, while its role in OSCC is unknown. Methods All participants were selected at Jiangxi Province Tumor Hospital from December 2016 to December 2018. Expression levels of NCK1-AS1 and miR-100 in plasma from both OSCC and OU patients were measured by RT-qPCR. Diagnostic analysis was performed through ROC curve. Potential interactions between NCK1-AS1 and miR-100 were detected by cell transfection experiments. Cell invasion and migration were assessed by Transwell assays. Results The expression of NCK1-AS1 was upregulated in early-stage OSCC patients but not in OU patients. Upregulation of NCK1-AS1 distinguished OSCC patients from OU patients. The expression of miR-100 was inversely correlated with the expression of NCK1-AS1. Overexpression of NCK1-AS1 was followed by promoted OSCC cell invasion and migration. Overexpression of miR-100 did not affect the expression of NCK1-AS1 but inhibited the role of NCK1-AS1. Conclusions Therefore, NCK1-AS1 may promote the metastasis of OSCC by downregulating miR-100.


2017 ◽  
Vol 13 (6) ◽  
pp. 4017-4026 ◽  
Author(s):  
Da Ma ◽  
Juan Fang ◽  
Ying Liu ◽  
Jing-Jing Song ◽  
Yan-Qiong Wang ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document