Circulating lncRNA as Biomarkers and Therapeutics in Oral Cancer: Silent Scripts with Loud Impact

Oral squamous cell carcinoma (OSCC) remains a major global health challenge due to late diagnosis, high recurrence, and limited therapeutic success. This review focuses on circulating long non-coding RNAs (lncRNAs) as emerging biomarkers and therapeutic targets that can transform the clinical management of OSCC. Unlike earlier studies restricted to tissue-based analyses, this work emphasizes circulating lncRNAs detectable in saliva, plasma, and serum, highlighting their non-invasive diagnostic potential and mechanistic relevance in tumor progression, metastasis, and therapy resistance. Relevant studies published up to 2025 were systematically reviewed from PubMed and Google Scholar to synthesize current knowledge on their biogenesis, secretion through extracellular vesicles and RNA-binding proteins, detection technologies, and clinical applicability. Several circulating lncRNAs, including HOTAIR, MALAT1, MEG3, ANRIL, and LINC00657, show strong associations with tumor stage, prognosis, and therapeutic outcomes. The review also discusses emerging RNA-based therapeutic approaches such as antisense oligonucleotides, RNA interference, and CRISPR-based gene editing. Overall, the analysis underscores the diagnostic precision, prognostic power, and therapeutic promise of circulating lncRNAs, proposing them as key components in the future of liquid biopsy-driven, personalized oncology for OSCC.