EBV-Induced LINC00944: A Driver of Oral Cancer Progression and Influencer of Macrophage Differentiation

Oral squamous cell carcinoma (OSCC) is a significant global health concern. Epstein-Barr virus (EBV) infection as well as long non-coding RNA (lncRNAs) associated EBV infection, have been linked to OSCC development and are known to influence cancer progression. <i>LINC00944</i> is associated with various cancers and immune cells, but its role in oral cancer remains underexplored. This study investigated the role of EBV-induced <i>LINC00944</i> in OSCC and its impact on the tumor microenvironment. The <i>LINC00944</i> expression was analyzed from a database of head and neck squamous cell carcinoma (HNSCC) tissues, and its expression in EBV-positive and EBV-negative OSCC cell lines was examined via qRT-PCR. We overexpressed <i>LINC00944</i> in SCC25 and ORL-48T oral cancer cell lines and evaluated its impact on migration and invasion ability using wound healing and transwell experiments. Additionally, we studied its influence on macrophage differentiation. The results showed that <i>LINC00944</i> expression was higher in HNSCC than in normal tissues and was linked to EBV-positive OSCC cell lines. <i>LINC00944</i> overexpressed-OSCC cell lines significantly increased cellular motility and invasiveness. Additionally, <i>LINC00944</i> was secreted in a cultured medium, delivered to macrophages, and promoted macrophage differentiation into the M1 subtype. Predicted interactions suggested that <i>LINC00944</i> targets miRNAs that regulate <i>NFKB1</i> and <i>RELA</i>. In conclusion, EBV-induced <i>LINC00944</i> contributes to OSCC progression by enhancing tumor cell migration, invasion, and macrophage differentiation, potentially regulating these processes through <i>NFKB1</i> and <i>RELA</i>. These findings provide valuable directions for <i>LINC00944</i>'s future studies on its mechanisms and suggest that it could be a target of study in EBV-associated OSCC.