Research progress of long non-coding RNAs in esophageal squamous cell carcinoma

This review provides a comprehensive framework for understanding the complex regulatory networks of long non-coding RNAs (lncRNAs) in esophageal squamous cell carcinoma (ESCC). We systematically summarize the multifaceted functions of lncRNAs in ESCC, highlighting their involvement in epigenetic remodeling, competitive endogenous RNA (ceRNA) networks, protein function modulation, tumor microenvironment communication, and the newly discovered capacity for encoding functional micropeptides. We delineate the dichotomous roles of lncRNAs as tumor promoters and suppressors, exemplified by molecules such as lnc191, PCAT1, HOTAIR, and BANCR driving oncogenic pathways, while others, such as MEG3, GAS5, and ADAMTS9-AS2, exert tumor-suppressive effects through integrated nuclear and cytoplasmic regulatory mechanisms. Furthermore, we explore the pivotal roles of lncRNAs in modulating therapeutic responses, where they affect the efficacy of chemotherapy, immunotherapy, and radiotherapy. Additionally, the potential of both individual lncRNAs and multi-lncRNA signatures as prognostic biomarkers is evaluated, underscoring their ability to stratify patient risk and predict outcomes. In conclusion, lncRNAs serve as important regulators in ESCC, operating through diverse multilayered mechanisms; however, clinical translation remains limited. Addressing challenges such as the lack of standardized detection methods will be essential to realize their potential as biomarkers and therapeutic targets in ESCC.