The regulatory role of HOX interacting lncRNA in oral cancer—An in silico analysis

Objectives: We aim to elucidate the interaction of long noncoding RNAs with HOX genes and their regulatory role and potential drug candidates in oral cancer. Materials and Methods: The interaction network was constructed using RNA Interactome and the RNA Interactome from the Sequencing Experiments database. The differential expression of HOX genes and HOX interacting lncRNAs was assessed using the TCGA-Head and Neck Squamous Cell Carcinoma oral cancer dataset using DESeq2 R-package. Further, the functional enrichment analysis was performed for the differentially expressed HOX genes and HOX-interacting lncRNAs using Gene Ontology, long noncoding RNA Set Enrichment Analysis, lncRNA ontology annotation extractor and repository (Lantern), and LncRNA Ontology tools. Drug-lncRNA interaction and the effect of drugs on lncRNA expression were assessed from the D-lnc tool. Results: A total of 78 unique interactions were identified between HOX and lncRNAs. Differential expression analysis showed 27 HOX genes and 10 HOX-interacting lncRNAs in oral cancer. HOX genes and HOX-interacting lncRNAs were involved in crucial regulatory processes like cell cycle regulation, cell proliferation and migration, epithelial-mesenchymal transition, angiogenesis, and cell signaling pathways. Cancer hallmark analysis from using long noncoding RNA Set Enrichment Analysis showed the involvement of HOTAIR, HOTTIP MIR503HG, and CDKN2B-AS1 in proliferation, migration, and invasion. Panobinostat was the common drug that influenced the expression of HOTAIR, HOTAIRM1, HOTTIP and CDKN2B-AS1. Conclusions: Differentially expressed HOX-interacting lncRNAs are involved in various regulatory biological processes and cancer hallmark events in oral cancer. Clinical Relevance: The creation of interaction networks may expand the existing knowledge of oral cancer signaling pathways and the discovery of novel targets.