The laryngeal squamous cell carcinoma (LSCC) represents a malignant cancer and contributes largely to head and neck tumorigenesis. The molecular mechanisms for LSCC progression are poorly understood. In current work, we identified long non-coding RNA (IncRNA) termed suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) as an oncogenic factor in LSCC. ST7-AS1 is frequently overexpressed in LSCC tissues and cell lines. ST7-AS1 is required for the malignancy of LSCC cells through migration, tumor sphere formation assay and in vivo implantation. Mechanistically, ST7-AS1 could interact with CARM1, a well characterized protein arginine methyltransferase and protect CARM1 from ubiquitin-dependent degradation. CARM1 can methylate Sox-2, a pluripotent transcription factor. Thus, ST7-AS1 might mediate its oncogenic effect by signaling through CARM1-Sox-2 axis to enhance Sox-2 self-association and transactivation activity. Collectively, we have unraveled a ST7-AS1/CARM1/Sox-2 signaling axis in LSCC and may have created novel interconnections between noncoding RNAs and cancer development. (C) 2019 Elsevier Inc. All rights reserved.