Linc-ROR orchestrates autophagy suppression and marks gastric cancer via the miR-145-5p/CARMIL1 axis.

Long non-coding RNAs (lncRNAs) have been considered the main regulators of cancer progression through their regulation of diverse cellular processes. Autophagy, which exerts context-dependent dual effects on gastric cancer (GC), remains controversial, and its interplay with lncRNAs has yet to be fully elucidated. Through integrated in vitro and in vivo functional assessments, we illustrate that silencing Linc-ROR markedly inhibits GC cell proliferation, migration, invasion, and xenograft growth. Transmission electron microscopy and mRFP-GFP-LC3 dual-fluorescence reporters revealed that Linc-ROR overexpression suppresses autophagic flux, which was further confirmed by Western blot analysis. Mechanistically, Linc-ROR functions as a competing endogenous RNA (ceRNA) to sequester miR-145-5p, thereby upregulating CARMIL1 and activating ERK/mTOR signaling, leading to autophagy inhibition and promotion of GC cell growth and invasiveness. Notably, pharmacological inhibition of mTOR with Everolimus reversed these malignant phenotypes, highlighting a therapeutically actionable vulnerability. Clinically, serum exosomal Linc-ROR was significantly elevated in GC patients and outperformed carcinoembryonic antigen (CEA) in diagnostic accuracy. Collectively, our findings establish Linc-ROR as a master regulator of autophagy suppression and GC progression via the miR-145-5p/CARMIL1/ERK-mTOR axis, underscoring its potential as a therapeutic target, while serum exosomal Linc-ROR emerges as a promising noninvasive biomarker for GC.