LOC730101 transmitted by exosomes facilitates laryngeal squamous cell carcinoma tumorigenesis via regulation of p38 MAPK gamma

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a prevalent human cancer with a complex pathogenesis that remains incompletely understood. Here, we unveil a long non-coding RNA (lncRNA) associated with LSCC tumorigenesis and progression. LOC730101 exhibits significant overexpression in human LSCC tissues, and elevated LOC730101 levels correlate with malignant clinicopathological characteristics. Moreover, we demonstrate that LOC730101 is encapsulated into exosomes in an hnRNPA2B1-dependent manner, serving as a promising plasma biomarker for discriminating LSCC patients from healthy individuals (AUC = 0.92 with 89.36% sensitivity and 86.36% specificity). Exosomes derived from LSCC cells enhance the viability, DNA synthesis rate, and invasiveness of normal nasopharynx epithelial cells, with pronounced effects observed upon LOC730101 overexpression. Additionally, exosomal LOC730101 promotes tumor growth in vivo. Mechanistically, exosomal LOC730101 internalization by normal nasopharynx epithelial cells leads to increased H3K4me3 levels on the p38 MAPK gamma (p38γ) promoter via direct interaction with hnRNPA2B1. This interaction activates p38γ transcription, ultimately driving LSCC tumorigenesis. Collectively, our findings uncover a novel exosomal lncRNA that mediates communication between normal and LSCC cells during LSCC carcinogenesis, suggesting that targeting LOC730101 may represent a promising therapeutic strategy for LSCC treatment.