Abstract 1485: Identification and in vitro validation of miRNA biomarker candidates in head and neck squamous cell carcinoma using a network biology approach

Abstract

Abstract Micro-RNAs are small non-coding RNAs that are able to modulate the gene expression. Aberrant expression of micro-RNAs leads to different diseased conditions such as cancer. Head and Neck Squamous Cell Carcinoma (HNSCC) is the second most prevalent cancer in Pakistan and contributes to 9.1% of mortality annually due to late stage diagnosis and ineffective treatment. This research attempts to identify novel miRNAs candidates for their potential role as diagnostic, prognostics or therapeutic biomarkers in HNSCC patient-derived primary cells in the Pakistani population. miRNA species and their gene targets reported in HNSCC were identified using the miRbase, miRNet, and miRCancer databases, and a total of 69 miRNAs with differential expression levels in HNSCC were selected to seed a miRNA-Gene interaction network that was created using BioGrid and STRING data. Hub genes that were targeted by over-expressed miRNAs were predicted using miRTarbase. GO and KEGG analysis was carried out for the 181 interacting genes including TP53, SMAD4, PTEN, NOTCH2, and STAT3. Enrichment analysis demonstrated the increased involvement of these miRNAs in Cancer Pathways such as Hippo signaling Pathways and FoxO signaling pathways. We prioritized hub genes that were targeted by the highest number of tumor suppressor genes, and identified five miRNA species, including miR-21-5p, miR-16-5p, miR30a-5p, miR-93-5p, and miR106b-5p, as the best biomarker candidates for experimental validation. To validate the in silico findings, the top five microRNA candidates are being screened for expression in a library of local patient-derived primary cell lines from Pakistani HNSCC patients. Citation Format: Laiba Shah, Maryam Shah, Abdus Salam, Khudeja Salim, Faisal F. Khan. Identification and in vitro validation of miRNA biomarker candidates in head and neck squamous cell carcinoma using a network biology approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1485.