A circGLIS3/miR-644a/PTBP1 positive feedback loop promotes the malignant biological progressions of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a severe cancer which critically threatens human health in the world. Circular RNAs (circRNAs) are non-coding RNAs that involve in cancer progression. We want to explore the roles of circRNAs in NSCLC in this study. In current study, circGLIS3 was found to be highly expressed in NSCLC tissues and cell lines and high circGLIS3 level was correlated to malignant characteristics and poor prognosis of NSCLC. Functional experiments suggested that circGLIS3 promoted proliferation, migration and invasion and arrested apoptosis of NSCLC cells in vitro. CircGLIS3 also participated in the in vivo process by accelerate NSCLC tumor growth and metastasis. Mechanistically, circGLIS3 could sponging multiple anti-cancer miRNAs including miR-526b, miR-198, miR-498 and miR-664a. Here, we for the first time confirmed that miR-644a was downregulated and functioned as a tumor suppression gene in NSCLC. In addition, we found PTBP1 as a novel target of miR-644a and circGLIS3 could raise the expression of PTBP1 via miR-644a. And PTBP1 could bind to the flanking introns of circGLIS3 and thereby promoting looping of circGLIS3. In conclusion, CircGLIS3 functions as an oncogene via sponging multiple tumor-suppressive miRNAs in NSCLC. A circGLIS3/miR-644a/PTBP1 positive feedback loop exists in the tumorigenesis and development of NSCLC. AJCR