Circular RNA hsa_circ_0018189 drives non-small cell lung cancer growth by sequestering miR-656-3p and enhancing xCT expression

Background: Non-small cell lung cancer (NSCLC) is one of the cancers with a high mortality rate. CircRNAs have emerged as an important regulatory factor in tumorigenesis in recent years. However, the detailed regulatory mechanism of a circular RNA cullin 2 (hsa_circ_0018189; hsa_circ_0018189) is still unclear in NSCLC.

Methods: RNA levels of hsa_circ_0018189, microRNA (miR)-656-3p, and Solute carrier family seven member 11 (SLC7A11, xCT) were analyzed by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and protein level was assessed by Western blot and immunohistochemical assay. Enzyme-linked immunosorbent assay was conducted to detect cell glutamine metabolism. Effects of hsa_circ_0018189 on cell proliferation, apoptosis, migration, and invasion were analyzed by corresponding assays. Luciferase reporter assay and RNA-immunoprecipitation assay confirmed the target relationship between miR-656-3p and hsa_circ_0018189 or xCT. The in vivo function of hsa_circ_0018189 was verified by xenograft mouse models.

Results: Hsa_circ_0018189 abundance was overexpressed in NSCLC cells and samples. Deficiency of hsa_circ_0018189 lowered NSCLC cell proliferative, migrating, invading, and glutamine metabolism capacities, and hsa_circ_0018189 silencing inhibited the growth of tumors in vivo. Hsa_circ_0018189 could up-regulate xCT by sponging miR-656-3p. And miR-656-3p downregulation or xCT overexpression partly overturned hsa_circ_0018189 knockdown or miR-656-3p mimic-mediated repression of NSCLC cell malignancy.

Conclusion: Hsa_circ_0018189 drove NSCLC growth by interacting with miR-656-3p and upregulating xCT.