hsa_circ_0006677 suppression of stemness and progression of non-small cell lung cancer by sponging miR-1276-induced ferroptosis in lung cancer stem cells

Abstract

Abstract The relationship between circRNAs (circRNAs) and lung cancer stem cells (LCSCs) is uncertain. Screening for relevant circRNAs through the GEO database. We investigated the impact of LCSCs and circRNA (hsa_circ_0006677) in the progression and treatment of NSCLC. We constructed lung CSCs (LCSCs; PC9 and A549). hsa_circ_0006677's role in vitro was determined by cell counting, clone and sphere formation, and Transwell analysis. Metastatic tumor xenograft models and in situ transplant models were established for in vivo analysis. We found that hsa_circ_0006677 was significantly low expressed in NSCLC tissues and LCSCs. hsa_circ_0006677 levels correlated with the stage and survival of NSCLC patients. hsa_circ_0006677 reduced levels decreased tumor cell proliferation, migration, invasion, and stem cell-like properties. Through the TRCirc database and in vivo and in vitro experiments hsa_circ_0006677 was positively regulated by GABPA. Meanwhile, downward continuous exploration by databases such as miRANDA database and validation with in vivo and in vitro experiments demonstrated that silencing of hsa_circ_0006677 was found to downregulate ATF3 expression and its ferroptosis signaling pathway by increasing the sponge effect of miR-1276. Our data demonstrate an important role for hsa_circ_0006677 in the stem cell-like properties of NSCLC cells. The key targets we identified in this signaling pathway, GABPA, hsa_circ_0006677, and miR-1276, may all intervene in the stemness and progression of NSCLC, which may also provide directions and ideas for future clinical treatments.