Circular RNA F-circSR derived from SLC34A2-ROS1 fusion gene promotes cell migration in non-small cell lung cancer

• Published in: Molecular cancer Vol. 18; no. 1; p. 98
• Main Authors: Wu, Ke, Liao, Xun, Gong, Youling, He, Juan, Zhou, Jian-Kang, Tan, Shuangyan, Pu, Wenchen, Huang, Canhua, Wei, Yu-Quan, Peng, Yong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22-05-2019; BioMed Central; BMC
• Subjects: A549 Cells; Binding sites; Bioinformatics; Biomarkers; Biopsy; Biosynthesis; Cancer cells; Cancer genetics; Carcinoma, Non-Small-Cell Lung - genetics; Cell adhesion & migration; Cell fusion; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement; Cell proliferation; Chromosome translocations; Circular RNA; Experiments; Fusion protein; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genetic research; Humans; Journalists; Letter to the Editor; Leukemia; Lung cancer; Lung Neoplasms - genetics; Non-small cell lung cancer; Non-small cell lung carcinoma; Novels; NSCLC; Oncogene Proteins, Fusion - genetics; Plasmids; Protein-Tyrosine Kinases - genetics; Proteins; Proto-Oncogene Proteins - genetics; Ribonucleic acid; RNA; RNA, Circular - genetics; SLC34A2-ROS1; Small cell lung cancer; Sodium-Phosphate Cotransporter Proteins, Type IIb - genetics; Splicing; Translocation, Genetic; Tumorigenesis; Tumors; Up-Regulation; Wound healing; SLC34A2-ROS1; Circular RNA; NSCLC; Cell migration
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-019-1028-9

Cancer-associated chromosomal translocations are reported to generate oncogenic circular RNA (circRNA), contributing to tumorigenesis. The fusion gene SLC34A2-ROS1 (solute carrier family 34 member 2 and ROS proto-oncogene 1) plays an important role in non-small cell lung cancer (NSCLC) progression. However, whether SLC34A2-ROS1 gene can produce circRNA remains unknown. Here, we identified two novel circRNAs (F-circSR1 and F-circSR2) generated from SLC34A2-ROS1 fusion gene, while F-circSR1 has higher expression than F-circSR2. Functional studies through gain- and loss-of-function strategies showed that both F-circSRs promote cell migration in lung cancer cells, whereas they have little effect on cell proliferation. Using the minigene GFP reporter assay, we verified that the flanking complementary sequences with canonical splicing sites are essential for F-circSR biogenesis. Therefore, our findings demonstrate the oncogenic role of F-circSR in NSCLC and highlight its therapeutic potential.