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.

In silico interaction of HOX cluster-embedded microRNAs and long non-coding RNAs in oral cancer.

The essential role HOX-associated non-coding RNAs play in chromatin dynamics and gene regulation has been well documented. The potential roles of these microRNAs and long non-coding RNAs in oral cancer development, with their attendant involvement in various cellular processes including proliferation, invasion, migration, epithelial-mesenchymal transition and metastasis is gaining credence. An interaction network of HOX-embedded non-coding RNAs was constructed to identify the RNA interaction landscape using the arena-Idb platform and visualized using Cytoscape. The miR-10a was shown to interact with HOXA1, miR-10b with HOXD10, miR-196a1 with HOXA5, HOXA7, HOXB8, HOXC8, HOXD8, and miR-196a2 with HOXA5. The lncRNAs, HOTAIR interacted with HOXC11, HOTAIRM1 with HOXA1 and HOXA4, HOTTIP with HOXA13, HOXA-AS2 with HOXA3, HOXA11-AS with HOXA11 and HOXD-AS1 with HOXB8. Changes in the HOX cluster-embedded non-coding RNAs have implications for prognosis and overall disease survival. Our review aims to analyze the functional significance and clinical relevance of non-coding RNAs within the HOX cluster in the context of oral carcinogenesis. Elucidating these interactions between the non-coding RNAs and HOX genes in oral cancer development and progression could pave the way for the identification of reliable biomarkers and potential therapeutic targets.