Expression of miR-655 in Oral Squamous Cell Carcinoma: A Bioinformatics Analysis
Wang Fengjuan 1, Du Wen 1, Li Hongfu 1, Du Yanxiao 2,3*
1 Diagnosis and Treatment Center, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao 266000, China
2 The Second Affiliated Hospital of Guangdong Medical University, Guangdong Medical University
3 Institute of Applied Chemistry, Chinese Academy of Sciences, Weigao Group Company Limited; Emil: duyanxiao2005@hotmail.com
Abstract: Oral squamous cell carcinoma (OSCC) is a common malignant tumor, which lies in the oral and maxillofacial region and is a serious threat for patients’ health and quality of life. MicroRNAs (miRNAs) play a crucial role in tumorigenesis and development. This study is expressed to investigate the expression of miR-655 in oral squamous cell carcinoma and its potential biological functions through bioinformatics analysis. Multiple bioinformatics databases, such as miRDB, The Cancer Genome Atlas (TCGA), and TargetScan, were used to analyze the differential expression of miR-655 in OSCC tissues versus normal tissues and to predict its target genes. By analyzing the functional enrichment of target genes, the biological processes and signaling pathways that miR-655 may be involved in were revealed. The results showed that miR-655 was abnormally expressed in oral squamous cell carcinoma tissues, and its target genes were mainly enriched in biological processes, which contains cell proliferation, apoptosis, migration, invasion, as well as signaling pathways related to tumorigenesis and development. This study provides a theoretical basis for further in-depth study of the mechanism of miR-655 in oral squamous cell carcinoma, and also provides potential biomarkers and therapeutic targets for the diagnosis and treatment of OSCC.
Keywords: oral squamous cell carcinoma; miR-655; bioinformatics analysis; target genes
Introduction
Oral squamous cell carcinoma is the most common malignant tumor of the oral and maxillofacial region, and its incidence is increasing year by year [1-5]. Although comprehensive treatments such as surgery, radiotherapy and chemotherapy have improved the survival rate of OSCC patients to a certain extent, the prognosis is still poor due to the difficulty of early diagnosis of OSCC, and most of the patients are already in the advanced stage when they are diagnosed [6-11]. Therefore, finding effective biomarkers for early diagnosis and prognosis assessment of OSCC and developing new therapeutic targets are of great clinical importance [12-18].
MicroRNAs (miRNAs) are a class of non-coding RNA molecules about 22 nucleotides in length, which regulate gene expression at the post-transcriptional level by complementary base pairing with target mRNAs [19-22]. More and more studies have shown that miRNAs play a key role in tumorigenesis, progression, invasion and metastasis. As a member of the miRNA family, miR-655 has been reported to be aberrantly expressed in a variety of tumors and involved in regulating the biological behavior of tumor cells [23-25]. However, the expression and mechanism of action of miR-655 in oral squamous cell carcinoma are still unclear [26].
In this study, we analyzed the expression of miR-655 in oral squamous cell carcinoma by bioinformatics methods, predicted its potential target genes, and preliminarily explored the biological function of miR-655 in OSCC by functional enrichment analysis of target genes, which provided a theoretical basis for further research on the mechanism of miR-655’s role in OSCC.
Materials and Methods
2.1 Data sources
The miRNA expression profile data of oral squamous cell carcinoma tissues and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Meanwhile, the prediction information of miR-655 target genes was obtained from miRDB (http://mirdb.org/) and TargetScan (http://www.targetscan.org/vert_72/) databases.
2.2 Differential expression analysis of miR-655 in OSCC tissues
The miRNA expression profile data downloaded from the TCGA database were processed and analyzed using R language software. Through differential expression analysis, miRNAs that were differentially expressed between oral squamous cell carcinoma tissues and normal tissues, including miR-655, were screened out. miR-655 was analyzed by differential expression analysis using the limma package, and the criterion for differential expression was set as fold change > 2 and P < 0.05.
2.3 Prediction of miR-655 target genes
The potential target genes of miR-655 were obtained based on the prediction results of miRDB and TargetScan database. To improve the accuracy of prediction, only genes that were predicted as miR-655 target genes in both databases were retained for subsequent analysis.
Results
3.1 GO analysis
The results of GO analysis show that the target genes of miR-655 are mainly enriched in biological processes such as cell proliferation, apoptosis, migration, invasion and cell cycle regulation; in terms of cellular components, they are mainly enriched in the cell membrane, cytoplasm and nucleus; in terms of molecular functions, they are mainly enriched in functions such as protein binding, nucleic acid binding and enzyme activity regulation.
3.2 KEGG pathway analysis
The results of KEGG pathway analysis show that the target genes of miR-655 are mainly involved in signaling pathways related to tumorigenesis and development, such as PI3K-Akt signaling pathway, MAPK signaling pathway, Wnt signaling pathway and Notch signaling pathway. These signaling pathways play crucial roles in cell proliferation, differentiation, apoptosis, migration and invasion, suggesting that miR-655 may affect the biological behavior of oral squamous cell carcinoma cells by regulating these signaling pathways.
Discussion
In this study, bioinformatics analysis revealed that miR-655 was highly expressed in oral squamous cell carcinoma tissues, and its target genes were mainly enriched in biological processes and signaling pathways closely related to tumorigenesis and development.
The high expression of miR-655 in OSCC tissues may promote the progression of oral squamous cell carcinoma by promoting the proliferation, migration and invasion of tumor cells and inhibiting apoptosis. For example, in the PI3K-Akt signaling pathway, miR-655 may activate this signaling pathway by regulating its target genes, which in turn promotes tumor cell survival and proliferation. In the MAPK signaling pathway, miR-655 may regulate cell growth, differentiation and apoptosis by affecting the expression of relevant target genes.
The results of this study provide important clues for further investigation of the mechanism of miR-655 in oral squamous cell carcinoma. However, the bioinformatics analysis is only a preliminary prediction and still needs to be validated by experiments, such as luciferase reporter gene assay and cell function assay, to determine the direct interaction between miR-655 and its target genes and the specific effects of miR-655 on the biological behavior of oral squamous cell carcinoma cells.
In addition, miR-655, as a potential biomarker, is expected to be used for early diagnosis, prognostic assessment and treatment monitoring of oral squamous cell carcinoma. Meanwhile, the development of new therapeutic strategies, such as miR-655 inhibitors or target gene activators, using miR-655 and its target genes as therapeutic targets may provide new avenues for the treatment of oral squamous cell carcinoma.
OSCC is a type of malignant tumor that poses a serious threat to human health. Due to the difficulty in early diagnosis and rapid progression of OSCC, its prognosis is poor [27-30]. The current pathogenesis of OSCC may involve multiple pathways, gene regulation, environmental factors, and other complex biological processes. MiRNA, as a non coding RNA with regulatory functions, can serve as a potential biomarker for the diagnosis and treatment of tumors during their occurrence and development. This study found through mining high-throughput sequencing data of OSCC that miR-655 is lowly expressed in OSCC tissues, and the high expression group of miR-655 in OSCC patients has better tumor grading and prognosis than the low expression group, suggesting the anticancer effect of miR-655 in OSCC. At present, there are no reports in China on the clinical expression and prognosis of miR-655 in OSCC. However, as a newly reported non coding RNA, miR-655 has been reported to be lowly expressed in some tumors and acts as a tumor suppressor gene. Gajera et al. reported that the expression of miR497-5p and miR-655 inhibits cell proliferation by regulating candidate genes for non syndromic cleft lip and palate in humans, providing a possible mechanism for the role of miRNA in the etiology of non syndromic cleft lip and palate, and proposing a possible strategy for diagnosing non syndromic cleft lip and palate. Zha et al. reported that miR-655 may inhibit the proliferation and invasion of ovarian cancer cells by regulating the expression of VEGF. Therefore, the miR-655/VEGF pathway can serve as a novel therapeutic target for ovarian cancer patients. Oshima and other studies suggest that the co delivery of tumor targeting miR-655 and oxaliplatin via nanoparticles inhibits the growth of liver cancer, suggesting that the use of tumor specific nanoparticles to co deliver microRNA and conventional cytotoxic agents can potentially treat metastatic liver cancer. This study used big data mining to discover that miR-655 is lowly expressed in OSCC tissues, and verified its expression in OSCC patients through qRT PCR, which is consistent with the above research results. Therefore, it is speculated that miR-655 has an inhibitory effect on tumors in OSCC. In further analysis, the correlation between miR-655 and tumor grading and prognosis in OSCC patients was explored for the first time. It was found that patients with high miR-655 expression had significantly better overall survival rates than those with low expression, and were negatively correlated with tumor grading. Cox regression analysis suggests that the expression level of miR655 is an independent factor in the prognosis of OSCC patients. A study has found that low levels of miR-655 in plasma are associated with lymphatic infiltration and poor prognosis. The recovery of miR-655 levels in plasma may inhibit lymphatic progression in esophageal squamous cell carcinoma and improve prognosis. Zhao et al. confirmed that low expression of miR-655 is associated with liver cancer.
Conclusion
In this study, bioinformatics analysis revealed that miR-655 is highly expressed in oral squamous cell carcinoma tissues, and its target genes are involved in a variety of biological processes and signaling pathways associated with tumorigenesis and development. These results provide a theoretical basis for an in-depth study of the mechanism of miR-655 in oral squamous cell carcinoma, as well as potential biomarkers and therapeutic targets for the diagnosis and treatment of OSCC. Further experimental studies are needed in the future to validate the results of bioinformatics analysis and to explore the clinical application value of miR-655 in oral squamous cell carcinoma.
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