scholarly journals Identification for Exploring Underlying Pathogenesis and Therapy Strategy of Oral Squamous Cell Carcinoma by Bioinformatics Analysis

2019 ◽  
Vol 25 ◽  
pp. 9216-9226
Author(s):  
Zheng Xu ◽  
Pan Jiang ◽  
Shengteng He
Author(s):  
Yuanhe You ◽  
Zhuowei Tian ◽  
Zhong Du ◽  
Kailiu Wu ◽  
Guisong Xu ◽  
...  

Abstract Background Tumor-associated macrophages (TAMs) have a leading position in the tumor microenvironment. Previously, we have demonstrated that M1-like TAMs activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma (OSCC). However, the functional roles and associated molecular mechanisms of the activated M1-like TAMs need to be further clarified in OSCC. Methods Conditioned Media (CM) were harvested from the exosome activated M1-like TAMs. We measured the malignant behaviors of OSCC under the treatment of CM from M1-like TAMs by performing colony forming assays, invasion assays, wound-healing assays, spheroid forming assays and in vivo xenograft experiments. The underlying mechanisms were investigated by RNA-seq, cytokines analysis, intracellular signaling pathway analysis, ChIP assays, bioinformatics analysis and validation. Results M1-like TAMs significantly promoted the epithelial-mesenchymal transition (EMT) process, and induced the cancer-stem like cells (CSCs) by upregulating the expression of MME and MMP14 in OSCC cells. Cytokine analysis revealed a shark increase of IL6 secretion from M1-like TAMs. Blocking IL6 in the CM from M1-like TAMs could significantly weaken its effects on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Cellular signaling assays indicated the activation of Jak/Stat3 pathway in the OSCC cells treated by the CM from M1-like TAMs. Blocking the activation of the Jak/Stat3 pathway could significantly weaken the effects of M1-like TAMs on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Further RNA-seq analysis and bioinformatics analysis revealed an increased expression of THBS1 in the OSCC cells treated by M1-like TAMs. Bioinformatics prediction and ChIP assays revealed the activation of Stat3 by CM from M1-like TAMs could directly promote the transcription of THBS1 in OSCC cells. Conclusions We proposed that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of OSCC via the IL6/Stat3/THBS1 feedback loop. A better understanding on the functional roles and associated molecular mechanisms of M1-like TAMs might facilitate the development of novel therapies for supplementing the current treatment strategies for OSCC patients.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11548
Author(s):  
Yin-Ling Wong ◽  
Anand Ramanathan ◽  
Kar Mun Yuen ◽  
Wan Mahadzir Wan Mustafa ◽  
Mannil Thomas Abraham ◽  
...  

Background Oral squamous cell carcinoma (OSCC) has increased in incidence from 1990 to 2017, especially in South and Southeast Asia. It is often diagnosed at an advanced stage with a poor prognosis. Therefore, early detection of OSCC is essential to improve the prognosis of OSCC. This study aims to identify the differentially expressed serum proteins as potential biomarkers for oral squamous cell carcinoma (OSCC). Methods Comparative proteomics profiling of serum samples from OSCC patients, oral potentially malignant disorder (OPMD) patients, and healthy individuals were performed using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS) (n = 60) and bioinformatics analysis. The enzyme-linked immunosorbent assay (ELISA) (n = 120) and immunohistochemistry (IHC) (n = 70) were used to confirm our findings. Results The 2-DE analysis revealed that 20 differentially expressed proteins were detected in OPMD and OSCC (p < 0.05). Bioinformatics analysis indicated that the activation of classical complement, liver X receptor/retinoid X receptor (LXR/RXR) activation, and acute phase response signaling pathway are associated with the development and progression of OSCC. Most of the detected proteins are acute-phase proteins and were related to inflammation and immune responses, including apolipoprotein A-I (APOA1), complement C3 (C3), clusterin (CLU), and haptoglobin (HP). The expression levels of CLU and HP in ELISA are consistent with the findings from the 2-DE analysis, except for the mean serum level of HP in OPMD, whereby it was slightly higher than that in control. IHC results demonstrated that CLU and HP are significantly decreased in OSCC tissues. Conclusion Decreased expression of CLU and HP could serve as complementary biomarkers of OSCC. These proteins may assist in predicting the outcomes of OSCC patients. However, a larger cohort is needed for further investigation.


2020 ◽  
Vol 21 (6) ◽  
pp. 1841-1848 ◽  
Author(s):  
Nasrin Amiri-Dashatan ◽  
Mehdi Koushki ◽  
Ali Jalilian ◽  
Nayeb Ali Ahmadi ◽  
Mostafa Rezaei Tavirani

2021 ◽  
Vol 63 (2) ◽  
pp. 174-178
Author(s):  
Tadashi Masaoka ◽  
Keiji Shinozuka ◽  
Kenshin Ohara ◽  
Hiromasa Tsuda ◽  
Kenichi Imai ◽  
...  

Author(s):  
Huijie Yu ◽  
◽  
Tianhua Li ◽  
Xuemei Mao ◽  
◽  
...  

Objective: To clear the expression of transcription factor Dickkopf-1 (DKK1) in Oral Squamous Cell Carcinoma (OSCC) using the method of bioinformatics analysis. And to clarify the relationship between the expression of DKK1 and the clinicopathological characteristics of OSCC using the method of molecular biology and cytobiology, in order to determine the early diagnosis and significance of OSCC according to the marker of DKK1. Methods: In this study, the expression level of DKK1 in OSCC tissues was analyzed using GEPIA and TCGA databases, and then verified in vitro by qRT-PCR and Western-blot analysis. The correlation between DKK1 gene expression and the clinical pathological parameters of OSCC, and also the impact of DKK1 on prognosis were determined using the Linked Omics database. In addition, DKK1 was knocked down by RNA interference in SCC-4 and SCC-25 OSCC cell lines and the proliferation ability of OSCC cells was assessed by MTT assay. Results: High expression of DKK1 in OSCC is positively correlated with the pathological grade and T stage of OSCC. According to the TCGA results, DKK1 mRNA was highly expressed and it is related to the overall survival rate of OSCC. In addition, the expression level of both DKK1mRNA and protein were significantly raised in the cell line SCC25 and SCC-4. Furthermore, MTT analysis showed that DKK1 knockdown resulted in reduced proliferation of OSCC cells. Conclusions: TCGA database analysis showed that DKK1 was highly expressed in OSCC, and it is closely correlated to the pathological parameters of OSCC, which will provide important theoretical guidance for the subsequent study of oral squamous cell carcinoma.


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