lncRNA HOTAIR in Cancer: Recent Advances and Critical Perspectives on Molecular Mechanisms

The long non-coding RNA (lncRNA) HOTAIR (HOX transcript antisense RNA) has emerged as an important regulatory molecule that plays a critical role in tumor initiation and progression. With advances in tumor molecular biology, HOTAIR has become a research focus owing to its high expression in multiple malignancies and its profound impact on key biological behaviors such as tumor cell proliferation, migration, invasion, and drug resistance. This review critically synthesizes recent advances, with a focus on mechanistic controversies, context-dependent functions, and the integration of epigenetic, non-coding RNA, and signaling network mechanisms. Current studies indicate that HOTAIR regulates diverse cellular functions and drives tumor progression mainly through epigenetic modification, modulation of key signaling pathways, and complex interactions with microRNAs (miRNAs). However, its precise molecular mechanisms have not yet been fully elucidated, and translation into clinical practice remains challenging. This review summarizes recent progress on HOTAIR in cancer, systematically outlines its multifaceted molecular mechanisms and functions, and discusses its potential as a diagnostic biomarker and therapeutic target, with the aim of providing a theoretical basis and research directions for precision diagnosis and treatment in oncology.