Yu-Jie Ning

Bio: Yu-Jie Ning is an academic researcher from Anhui Medical University. The author has contributed to research in topics: Head and neck squamous-cell carcinoma. The author has an hindex of 1, co-authored 1 publications receiving 2 citations.

The Biological Function, Mechanism, and Clinical Significance of m6A RNA Modifications in Head and Neck Carcinoma: A Systematic Review

Abstract: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, yet the molecular mechanisms underlying its onset and development have not yet been fully elucidated. Indeed, an in-depth understanding of the potential molecular mechanisms underlying HNSCC oncogenesis may aid the development of better treatment strategies. Recent epigenetic studies have revealed that the m6A RNA modification plays important roles in HNSCC. In this review, we summarize the role of m6A modification in various types of HNSCC, including thyroid, nasopharyngeal, hypopharyngeal squamous cell, and oral carcinoma. In addition, we discuss the regulatory roles of m6A in immune cells within the tumor microenvironment, as well as the potential molecular mechanisms. Finally, we review the development of potential targets for treating cancer based on the regulatory functions of m6A, with an aim to improving targeted therapies for HNSCC. Together, this review highlights the important roles that m6A modification plays in RNA synthesis, transport, and translation, and demonstrates that the regulation of m6A-related proteins can indirectly affect mRNA and ncRNA function, thus providing a novel strategy for reengineering intrinsic cell activity and developing simpler interventions to treat HNSCC.

HNRNPA2B1, as a m6A Reader, Promotes Tumorigenesis and Metastasis of Oral Squamous Cell Carcinoma.

Abstract: N6-methyladenosine (m6A) modification is the most prevalent modification on eukaryotic RNA, and the m6A modification regulators were involved in the progression of various cancers. However, the functions of m6A regulators in oral squamous cell carcinoma (OSCC) remain poorly understood. In this study, we demonstrated that 13 of 19 m6A-related genes in OSCC tissues are dysregulated, and HNRNPA2B1 was the most prognostically important locus of the 19 m6A regulatory genes in OSCC. Moreover, HNRNPA2B1 expression is elevated in OSCC, and a high level of HNRNPA2B1 is significantly associated with poor overall survival in OSCC patients. Functional studies, combined with further analysis of the correlation between the expression of HNRNPA2B1 and the EMT-related markers from the TCGA database, reveal that silencing HNRNPA2B1 suppresses the proliferation, migration, and invasion of OSCC via EMT. Collectively, our work shows that HNRNPA2B1 may have the potential to promote carcinogenesis of OSCC by targeting EMT via the LINE-1/TGF-β1/Smad2/Slug signaling pathway and provide insight into the critical roles of HNRNPA2B1 in OSCC.

Identification of a N6-Methyladenosine (m6A)-Related lncRNA Signature for Predicting the Prognosis and Immune Landscape of Lung Squamous Cell Carcinoma

Abstract: Background: m6A-related lncRNAs emerged as potential targets for tumor diagnosis and treatment. This study aimed to identify m6A-regulated lncRNAs in lung squamous cell carcinoma (LUSC) patients. Material and methods: RNA-sequencing and clinical data of LUSC patients were downloaded from the Cancer Genome Atlas (TCGA) database. m6A-related lncRNAs were identified by using Pearson correlation assay. Univariate the multivariate cox regression analyses were utilized to construct a risk model. The performance of the risk model was validated using Kaplan Meier survival analysis, receiver operating curve (ROC). Immune estimation of LUSC were downloaded from TIMER. And the correlations between the risk score and various immune cells infiltration were analyzed using various methods. Differences in immune functions, and expression of immune checkpoint inhibitors and m6A regulators between high risk and low risk groups were further explored. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to explore the biological functions of AL122125.1. Results: A total of 351 m6A-related lncRNAs were obtained from TCGA. Seven lncRNAs demonstrated prognostic values. Further multivariate cox regression assay constructed a risk model consisted of 2 lncRNAs (AL122125.1 and HORMAD2-AS1). Kaplan-Meier analysis and area under the curve (AUC) indicated that this risk model could be used to predict the prognosis of LUSC patients. The m6A-retaed lncRNAs were immune associated. There were significant correlations between risk score and immune cell infiltration, immune functions and expression of immune checkpoint inhibitors. Meanwhile, there were significant differences in the expression of m6A regulators between the high- and low-risk groups. Moreover, GO and KEGG analyses revealed that upregulated expression of AL122125.1 was tumor-related. Conclusion: In this study, we constructed a m6A-related lncRNA risk model to predict the survival of LUSC patients. This study could provide novel insight to the prognosis and treatment of LUSC patients.

Oral Squamous Cell Carcinoma Gene Patterns Connected with RNA Methylation for Prognostic Prediction.

Abstract: OBJECTIVES To determine whether m6A/m1A/m5C/m7G/m6Am/Ψ-related genes influence the prognosis of a patient with oral squamous cell carcinoma. MATERIALS AND METHODS We investigated the changes in regulatory genes using publicly available data from The Cancer Genome Atlas. Consensus clustering by RNA methylation-related regulators was used to describe oral squamous cell carcinomas (OSCCs). Then we developed the prediction model. The tumor microenvironment was investigated using ESTIMATE. Gene set enrichment analysis was used to determine whether pathways or cell types were enriched in different groups. The association between the model and immune-related risk scores was investigated using correlation analysis. RESULTS We found 22 gene signatures in this analysis and then developed a predictive model that reveals the genes that are highly connected to the overall survival of OSCC patients. The survival and death rates were substantially different in the two groups (high and low risk) classified by the risk scores. The validation cohort verified the phenotypic diversity and prognostic effects of these genes. CONCLUSION Our data reveal that immune cell infiltration, genetic mutation, and survival potential in OSCC patients are linked to m6A/m1A/m5C/m7G/m6Am/Ψ-related genes, and we constructed a dependable prognostic model for OSCC patients.

Shaping the Innate Immune Response Through Post-Transcriptional Regulation of Gene Expression Mediated by RNA-Binding Proteins

Abstract: Innate immunity is the frontline of defense against infections and tissue damage. It is a fast and semi-specific response involving a myriad of processes essential for protecting the organism. These reactions promote the clearance of danger by activating, among others, an inflammatory response, the complement cascade and by recruiting the adaptive immunity. Any disequilibrium in this functional balance can lead to either inflammation-mediated tissue damage or defense inefficiency. A dynamic and coordinated gene expression program lies at the heart of the innate immune response. This expression program varies depending on the cell-type and the specific danger signal encountered by the cell and involves multiple layers of regulation. While these are achieved mainly via transcriptional control of gene expression, numerous post-transcriptional regulatory pathways involving RNA-binding proteins (RBPs) and other effectors play a critical role in its fine-tuning. Alternative splicing, translational control and mRNA stability have been shown to be tightly regulated during the innate immune response and participate in modulating gene expression in a global or gene specific manner. More recently, microRNAs assisting RBPs and post-transcriptional modification of RNA bases are also emerging as essential players of the innate immune process. In this review, we highlight the numerous roles played by specific RNA-binding effectors in mediating post-transcriptional control of gene expression to shape innate immunity.

Single-cell transcriptomics uncover the key ferroptosis regulators contribute to cancer progression in head and neck squamous cell carcinoma

Abstract: The mechanism underlying the association between the development of head and neck squamous cell carcinoma (HNSCC) and ferroptosis is unclear. We analyzed the transcriptomes of 5902 single cells from a single-cell RNA-sequencing (scRNA-seq) dataset. They then aggregate into B cells, epithelial cells, fibroblasts, germ cells, mesenchymal cells, cancer stem cells, stem cells, T cells and endometrial cells, respectively. Our study shows that multiple pathways are significantly enriched in HNSCC development including extracellular matrix structural components, humoral immune responses, and muscle contraction. Differentially expressed genes analysis in Pseudotime analysis, pathway and biological function indicated that there was a significant correlation in the ferroptosis pathway. Furthermore, higher ferroptosis potential index (FPI) scores were significantly associated with worse overall survival prognosis in HNSCC patients. Pseudo-temporal, survival analyses and immunohistochemistry identified multiple central genes in HNSCC development, including ACSL1, SLC39A14, TFRC, and PRNP genes, and indicated associated ferroptosis. Overall, our study detected ferroptosis-related features is closely correlated with HNSCC prognosis and development, and deserved candidates suitable for immunotherapy treatment strategies determination for HNSCC patients.