Hsa_circ_0000515 sequesters microRNA-296-5p and elevates RNF44 expression to encourage the NSCLC progression

Abstract

Circular RNAs (circRNAs) are RNA molecules frequently involved in tumorigenesis. This research study focuses on the relevance of hsa_circ_515 (circ_515) to non-small cell lung cancer (NSCLC) progression and the downstream targets involved. Differentially expressed circRNAs in NSCLC were screened using a GSE158695 dataset. Circ_515 was overexpressed and indicated poor outcomes in patients with NSCLC. Knockdown of circ_515 repressed proliferation and invasiveness, while potentiated cell cycle arrest and apoptosis of NSCLC cells, and upregulation of circ_515 led to converse trends. The candidate downstream transcripts of circ_515 were explored using integrated bioinformatic analyses. Ectopic expression of miR-296-5p reduced the malignance of NSCLC cells. Circ_515 sequestered miR-296-5p and blocked its suppressive role in RING finger protein 44 (RNF44) expression. Downregulation of RNF44 counteracted the oncogenic effects of circ_515. In vivo, the anti-tumor effects of circ_515 knockdown were reversed by miR-296-5p, while the tumor-promoting effects of circ_515 upregulation were abolished by RNF44 knockdown. All in all, our findings demonstrate that circ_515 sequesters miR-296-5p and elevates RNF44 expression to encourage the NSCLC progression. This study might provide new thoughts on NSCLC management.