An integrated approach for identification of a panel of candidate genes arbitrated for invasion and metastasis in oral squamous cell carcinoma

AbstractOral squamous cell carcinoma (OSCC) is known for its aggressiveness associated with poor prognosis. The molecular mechanisms underlying the invasion and metastasis are still poorly understood. An improved understanding of these mechanisms shall precede the development of new diagnostic tools and targeted therapies. We report an integrated approach using bioinformatics to predict candidate genes, coupled with proteomics and immunohistochemistry for validating their presence and involvement in OSCC pathways heralding invasion and metastasis. Four genes POSTN, TNC, CAV1 and FSCN1 were identified. A protein–protein interaction network analysis teamed with pathway analysis led us to propose the role of the identified genes in invasion and metastasis in OSCC. Further analyses of archived FFPE blocks of various grades of oral cancer was carried out using TMT-based mass spectrometry and immunohistochemistry. Results of this study expressed a strong communiqué and interrelationship between these candidate genes. This study emphasizes the significance of a molecular biomarker panel as a diagnostic tool and its correlation with the invasion and metastatic pathway of OSCC. An insight into the probable association of CAF's and these biomarkers in the evolution and malignant transformation of OSCC further magnifies the molecular-biological spectrum of OSCC tumour microenvironment.

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Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

ISRN Oncology ◽

10.5402/2012/681469 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 21

Author(s):

Suttichai Krisanaprakornkit ◽

Anak Iamaroon

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathways ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Large Body ◽

Invasion And Metastasis ◽

Mesenchymal Transition

Oral cancer is one of the drastic human cancers due to its aggressiveness and high mortality rate. Of all oral cancers, squamous cell carcinoma is the most common accounting for more than 90%. Epithelial-mesenchymal transition (EMT) is suggested to play an important role during cancer invasion and metastasis. Recently, emerging knowledge on EMT in carcinogenesis is explosive, tempting us to analyze previous studies on EMT in oral squamous cell carcinoma (OSCC). In this paper, we have first addressed the general molecular mechanisms of EMT, evidenced by alterations of cell morphology during EMT, the presence of cadherin switching, turning on and turning off of many specific genes, the activation of various signaling pathways, and so on. The remaining part of this paper will focus on recent findings of the investigations of EMT on OSCC. These include the evidence of EMT taking place in OSCC and the signaling pathways employed by OSCC cells during their invasion and metastasis. Collectively, with the large body of new knowledge on EMT in OSCC elaborated here, we are hopeful that targeting treatment for OSCC will be developed.

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Identification of SPRR3 as a novel diagnostic/prognostic biomarker for oral squamous cell carcinoma via RNA sequencing and bioinformatic analyses

PeerJ ◽

10.7717/peerj.9393 ◽

2020 ◽

Vol 8 ◽

pp. e9393

Author(s):

Lu Yu ◽

Zongcheng Yang ◽

Yingjiao Liu ◽

Fen Liu ◽

Wenjing Shang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Tumor Marker ◽

Cell Carcinoma ◽

Candidate Genes ◽

Squamous Cell ◽

Prognostic Biomarker ◽

Interaction Network ◽

Normal Tissues ◽

Small Proline Rich Protein

Oral squamous cell carcinoma (OSCC) has always been one of the most aggressive and invasive cancers among oral and maxillofacial malignancies. As the morbidity and mortality of the disease have increased year by year, the search for a promising diagnostic and prognostic biomarker for the disease is becoming increasingly urgent. Tumorous and adjacent tissues were collected from three OSCC sufferers and we obtained 229 differentially expressed genes (DEGs) between tumor and normal tissues via high-throughput RNA sequence. Function and pathway enrichment analyses for DEGs were conducted to find a correlation between tumorigenesis status and DEGs. Protein interaction network and molecular complex detection (MCODE) were constructed to detect core modules. Two modules were enriched in MCODE. The diagnostic and prognostic values of the candidate genes were analyzed, which provided evidence for the candidate genes as new tumor markers. Small Proline Rich Protein 3 (SPRR3), a potential tumor marker that may be useful for the diagnosis of OSCC, was screened out. The survival analysis showed that SPRR3 under expression predicted the poor prognosis of OSCC patients. Further experiments have also shown that the expression of SPRR3 decreased as the malignancy of OSCC increased. Therefore, we believe that SPRR3 could be used as a novel diagnostic and prognostic tumor marker.

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Macrophage migration inhibitory factor promotes the invasion and metastasis of oral squamous cell carcinoma through matrix metalloprotein‐2/9

Molecular Carcinogenesis ◽

10.1002/mc.23067 ◽

2019 ◽

Vol 58 (10) ◽

pp. 1809-1821 ◽

Cited By ~ 2

Author(s):

Sha‐Sha Wang ◽

Min Zheng ◽

Xin Pang ◽

Mei Zhang ◽

Xiang‐Hua Yu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Invasion And Metastasis

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Long Non-Coding RNA (lncRNA) in Oral Squamous Cell Carcinoma: Biological Function and Clinical Application

Cancers ◽

10.3390/cancers13235944 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5944

Author(s):

Jianfei Tang ◽

Xiaodan Fang ◽

Juan Chen ◽

Haixia Zhang ◽

Zhangui Tang

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Non Coding Rna ◽

Potential Applications ◽

Non Coding Rnas ◽

Long Non Coding Rna

Oral squamous cell carcinoma (OSCC) is a type of malignancy with high mortality, leading to poor prognosis worldwide. However, the molecular mechanisms underlying OSCC carcinogenesis have not been fully understood. Recently, the discovery and characterization of long non-coding RNAs (lncRNAs) have revealed their regulatory importance in OSCC. Abnormal expression of lncRNAs has been broadly implicated in the initiation and progress of tumors. In this review, we summarize the functions and molecular mechanisms regarding these lncRNAs in OSCC. In addition, we highlight the crosstalk between lncRNA and tumor microenvironment (TME), and discuss the potential applications of lncRNAs as diagnostic and prognostic tools and therapeutic targets in OSCC. Notably, we also discuss lncRNA-targeted therapeutic techniques including CRISPR-Cas9 as well as immune checkpoint therapies to target lncRNA and the PD-1/PD-L1 axis. Therefore, this review presents the future perspectives of lncRNAs in OSCC therapy, but more research is needed to allow the applications of these findings to the clinic.

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N-α-Acetyltransferase 10 protein inhibits invasion and metastasis of oral squamous cell carcinoma via regulating Pirh2-p53 signaling pathway

10.21203/rs.3.rs-29042/v1 ◽

2020 ◽

Author(s):

Fazhan Wang ◽

Jun Zheng ◽

Yongyong Yang ◽

Jie Yang ◽

Ting Luo ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Squamous Cell ◽

Nude Mice ◽

Invasion And Metastasis ◽

P53 Signaling ◽

P53 Signaling Pathway

Abstract Background Naa10p (N-α-Acetyltransferase 10 protein) was reported to be involved in tumor invasion and metastasis in several of tumors. However, the role and mechanism of Naa10p mediated invasion and metastasis in oral squamous cell carcinoma (OSCC) remains undetermined. Methods The functional role of Naa10p in OSCC cells were determined using Transwell assay in vitro and xenograft tumorigenesis in nude mice. Immunoprecipitation, GST-pull down assays and immunofluorescence were performed to confirm the interaction between Naa10p and RelA/p65 in OSCC cells. Lastly, luciferase reporter assays, chromatin immunoprecipitation (ChIP) and western blot were used to evalute the effect of Naa10p expression on the Pirh2-p53 signaling pathway. Results Naa10p inhibits cell migration and invasion in vitro and attenuates the xenograft tumorigenesis in nude mice. Mechanistically, there is a physical interaction between Naa10p and RelA/p65 in OSCC cells, thereby preventing RelA/p65-mediated transcriptional activation of Pirh2. Consequently, inhibition of Pirh2 increased p53 level and suppressed the expression of p53 downstream targets, MMP-2 and MMP-9. Conclusion Naa10p function as a tumor metastasis suppressor in the progression of OSCC by targeting Pirh2-p53 axis, and might be a prognostic marker as well as a therapeutic target for OSCC.

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LncRNA HOTAIR promotes the invasion and metastasis of oral squamous cell carcinoma through metastasis‐associated gene 2

Molecular Carcinogenesis ◽

10.1002/mc.23159 ◽

2020 ◽

Vol 59 (4) ◽

pp. 353-364 ◽

Cited By ~ 5

Author(s):

Detao Tao ◽

Zhenxing Zhang ◽

Xue Liu ◽

Ziwen Zhang ◽

Yu Fu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Invasion And Metastasis ◽

Lncrna Hotair ◽

Metastasis Associated Gene

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NF-κB-mediated lncRNA AC007271.3 promotes carcinogenesis of oral squamous cell carcinoma by regulating miR-125b-2-3p/Slug

Cell Death and Disease ◽

10.1038/s41419-020-03257-4 ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Ze-nan Zheng ◽

Guang-zhao Huang ◽

Qing-qing Wu ◽

Heng-yu Ye ◽

Wei-sen Zeng ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Nuclear Factor Κb ◽

Underlying Mechanisms ◽

E Cadherin

AbstractOral squamous cell carcinoma (OSCC) is the most common oral cancer. The molecular mechanisms of this disease are not fully understood. Our previous studies confirmed that dysregulated function of long non-coding RNA (lncRNA) AC007271.3 was associated with a poor prognosis and overexpression of AC007271.3 promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. However, the underlying mechanisms of AC007271.3 dysregulation remained obscure. In this study, our investigation showed that AC007271.3 functioned as competing endogenous RNA by binding to miR-125b-2-3p and by destabilizing primary miR-125b-2, resulted in the upregulating expression of Slug, which is a direct target of miR-125b-2-3p. Slug also inhibited the expression of E-cadherin but N-cadherin, vimentin, and β-catenin had no obvious change. The expression of AC007271.3 was promoted by the canonical nuclear factor-κB (NF-κB) pathway. Taken together, these results suggested that the classical NF-κB pathway-activated AC007271.3 regulates EMT by miR-125b-2-3p/Slug/E-cadherin axis to promote the development of OSCC, implicating it as a novel potential target for therapeutic intervention in this disease.

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Peptide functionalized upconversion/NIR II luminescent nanoparticles for targeted imaging and therapy of oral squamous cell carcinoma

Biomaterials Science ◽

10.1039/d0bm01737j ◽

2021 ◽

Author(s):

Bi Lin ◽

Jun Wu ◽

Yanxing Wang ◽

Song Sun ◽

Ying Yuan ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Early Diagnosis ◽

Cell Carcinoma ◽

Squamous Cell ◽

Poor Prognosis ◽

Targeted Imaging ◽

Invasion And Metastasis ◽

High Incidence ◽

Luminescent Nanoparticles

Early diagnosis is critical and challenging for tongue squamous cell carcinoma (TSCC), which is a kind of tumor with high malignancy, poor prognosis, and a high incidence of invasion and metastasis.

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