Posters
Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: The prevalence of oral cancer worldwide is on the rise, with India accounting for almost a third of all documented cases. Despite significant progress in therapeutic approaches, elevated mortality rates and recurrent disease incidences pose a considerable challenge to India’s emerging healthcare sector. Hence, there is an urgent need to comprehend the underlying pathophysiology of oral cancer and devise innovative and effective therapeutic interventions for both prevention and treatment of this lethal ailment. TNFAIP8 is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of various malignancies. Therefore, targeting TNFAIP8 protein might be a crucial step in circumventing the oral carcinogenesis. MicroRNAs (miRNAs) being the master regulators of gene expression, are known to modulate the various hallmarks of oral tumorigenesis. Thus, the proposed study aims to identify significant miRNAs regulating TNFAIP8 protein and develop miRNA therapeutics for oral cancer treatment.
Methods: A comprehensive bioinformatics analysis for TNFAIP8 and the candidate miRNAs was undertaken using head and neck cancer (HNSC) datasets from different databases associating gene expression with various clinco-pathological attributes. Further, selected miRNAs were transfected in oral cancer cell lines and the functionality of the miRNA was assessed using different assays for establishing its therapeutic relevance.
Results: It was revealed that the expression of TNFAIP8 was significantly higher in HNSC patients in various databases, including GEO-HNSC (Gene Expression Omnibus-HNSC), TCGA-HNSC (The Cancer Genome Atlas-HNSC), and CPTAC-HNSC (Clinical Proteomic Tumor Analysis Consortium-HNSC). Moreover, utilizing web-based computational tools, seven potential miRNAs targeting TNFAIP8 were identified and subsequent analysis unveiled that the expression levels of five among these miRNAs exhibited significant downregulation in both TCGA-HNSC and CPTAC-HNSC datasets. Furthermore, qRT-PCR findings in different oral cancer cell lines were consistent with the in-silico analysis. Overexpression of hsa-miR-299-5p resulted in knockdown of TNFAIP8 with reduced proliferation, colony formation ability and autophagy with increased apoptosis in oral cancer cells. Further, miRNA-mediated knockdown of TNFAIP8 led to induction of S-phase arrest with increased levels of p-53 expression. It was also demonstrated that upregulation of hsa-miR-299-5p led to decreased invasion, migration and EMT of oral cancer cells. Moreover, mimics treatment inhibited the phosphorylation of NF-B and AKT, key signaling pathways in oral cancer development and progression. However, further studies are ongoing to elucidate the effect of hsa-miR-299-5p mimics AKT/mTOR and STAT3 pathways.
Conclusion: In various HNSC datasets, TNFAIP8 exhibited upregulation, while hsa-miR-299-5p was downregulated when compared with appropriate controls. Hsa-miR-299-5p, identified as a putative regulator of TNFAIP8, functioned as a tumor suppressor gene, suppressing various cancer hallmarks like proliferation, migration, invasion and autophagy. Hence, targeting the TNFAIP8/hsa-miR-299-5p axis presents a potential strategy to inhibit oral tumorigenesis.
Recommended Citation
Kumar, Aviral, "Development of miRNA mimics targeting tumor necrosis factor-α induced protein eight (TNFAIP8/TIPE) in oral cancer" (2024). Research Symposium. 78.
https://scholarworks.utrgv.edu/somrs/2024/posters/78
Included in
Development of miRNA mimics targeting tumor necrosis factor-α induced protein eight (TNFAIP8/TIPE) in oral cancer
Background: The prevalence of oral cancer worldwide is on the rise, with India accounting for almost a third of all documented cases. Despite significant progress in therapeutic approaches, elevated mortality rates and recurrent disease incidences pose a considerable challenge to India’s emerging healthcare sector. Hence, there is an urgent need to comprehend the underlying pathophysiology of oral cancer and devise innovative and effective therapeutic interventions for both prevention and treatment of this lethal ailment. TNFAIP8 is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of various malignancies. Therefore, targeting TNFAIP8 protein might be a crucial step in circumventing the oral carcinogenesis. MicroRNAs (miRNAs) being the master regulators of gene expression, are known to modulate the various hallmarks of oral tumorigenesis. Thus, the proposed study aims to identify significant miRNAs regulating TNFAIP8 protein and develop miRNA therapeutics for oral cancer treatment.
Methods: A comprehensive bioinformatics analysis for TNFAIP8 and the candidate miRNAs was undertaken using head and neck cancer (HNSC) datasets from different databases associating gene expression with various clinco-pathological attributes. Further, selected miRNAs were transfected in oral cancer cell lines and the functionality of the miRNA was assessed using different assays for establishing its therapeutic relevance.
Results: It was revealed that the expression of TNFAIP8 was significantly higher in HNSC patients in various databases, including GEO-HNSC (Gene Expression Omnibus-HNSC), TCGA-HNSC (The Cancer Genome Atlas-HNSC), and CPTAC-HNSC (Clinical Proteomic Tumor Analysis Consortium-HNSC). Moreover, utilizing web-based computational tools, seven potential miRNAs targeting TNFAIP8 were identified and subsequent analysis unveiled that the expression levels of five among these miRNAs exhibited significant downregulation in both TCGA-HNSC and CPTAC-HNSC datasets. Furthermore, qRT-PCR findings in different oral cancer cell lines were consistent with the in-silico analysis. Overexpression of hsa-miR-299-5p resulted in knockdown of TNFAIP8 with reduced proliferation, colony formation ability and autophagy with increased apoptosis in oral cancer cells. Further, miRNA-mediated knockdown of TNFAIP8 led to induction of S-phase arrest with increased levels of p-53 expression. It was also demonstrated that upregulation of hsa-miR-299-5p led to decreased invasion, migration and EMT of oral cancer cells. Moreover, mimics treatment inhibited the phosphorylation of NF-B and AKT, key signaling pathways in oral cancer development and progression. However, further studies are ongoing to elucidate the effect of hsa-miR-299-5p mimics AKT/mTOR and STAT3 pathways.
Conclusion: In various HNSC datasets, TNFAIP8 exhibited upregulation, while hsa-miR-299-5p was downregulated when compared with appropriate controls. Hsa-miR-299-5p, identified as a putative regulator of TNFAIP8, functioned as a tumor suppressor gene, suppressing various cancer hallmarks like proliferation, migration, invasion and autophagy. Hence, targeting the TNFAIP8/hsa-miR-299-5p axis presents a potential strategy to inhibit oral tumorigenesis.