Circ‐SOX4 promotes non‐small cell lung cancer progression by activating the Wnt/β‐catenin pathway

Non-small-cell lung carcinoma (NSCLC) accounts for the majority of lung cancer deaths, and thus there is a clinical need to understand the molecular mechanisms underlying this malignancy. Tumor-initiating cells (TICs) have been accepted to be closely related to tumor reoccurrence after surgery, and circular RNAs (circRNAs) play a crucial function in the tumorigenesis and development of human cancers. Here, we examined the role of the circular RNA hsa_circ_0131457 (circ-SOX4) in lung TICs. We report that circ-SOX4 is upregulated and exists as a covalently closed loop structure in CD133+ cancer cells. Subsequent functional assays showed that circ-SOX4 downregulation suppresses lung TIC proliferation, self-renewal, migration and invasion. Circ-SOX4 upregulation facilitates in vitro development of CD133- cancer cells, and circ-SOX4 deficiency represses in vivo malignancy of CD133+ cells. Additionally, circ-SOX4 was shown to interact with c-MYC by activating the Wnt/β-catenin pathway in NSCLC. In summary, circ-SOX4 expedites NSCLC progression by activating the Wnt/β-catenin pathway, and this finding may facilitate the identification of effective therapeutic targets for NSCLC.