Self-restricted circular RNA circSOX2 suppressed the malignant progression in SOX2-amplified LUSC

Abstract

Abstract Lung squamous cell carcinoma (LUSC) is a histological subtype of non-small cell lung cancer with the worse progression. SRY-Box Transcription Factor 2 (SOX2) copy number amplification (CNA) is the oncogenic driver in ~60% of patients diagnosed with LUSC. Thus, SOX2 represents an effective therapeutic target in SOX2-amplified LUSC. However, SOX2 protein was considered undruggable. Here, we report the expression of a circular RNA, cicSOX2 in SOX2-amplified LUSC. Patients with SOX2-CAN LUSC expressing circSOX2 manifested increased survival outcomes. CircSOX2 suppressed the proliferation, metastasis, and sphere formation in SOX2-amplified LUSC in vitro and in vivo. CircSOX2 originates in the reverse strand of the SOX2 gene and its sequence was reverse complement to partial 3’UTR of SOX2-coding transcript (mSOX2). CircSOX2 bound to AUF1 and occupied in the 3’UTR of mSOX2, inducing the degradation of mSOX2. In general, circSOX2 is an endogenous self-restricted circRNA in SOX2-amplified LUSC. CircSOX2 might be an effective and stable nucleic acid drug candidate in SOX2-amplified LUSC with low immunogenicity.