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

## TL;DR

This study shows that a circular RNA called circ_515 promotes non-small cell lung cancer by blocking a tumor-suppressing microRNA and increasing RNF44 protein levels.

## Contribution

The study identifies a novel circ_515/miR-296-5p/RNF44 regulatory axis in NSCLC progression.

## Key findings

- Circ_515 is overexpressed in NSCLC and linked to poor patient outcomes.
- Circ_515 promotes cancer cell growth and invasiveness by sequestering miR-296-5p and upregulating RNF44.
- Knockdown of circ_515 or RNF44 reduces tumor progression in NSCLC.

## 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.

In this study, a novel circular RNA_515 (circ_515)/microRNA‐296‐5p (miR‐296‐5p)/RING finger protein 44 (RNF44) axis is identified to be closely linked to the pathogenesis of non‐small cell lung cancer (NSCLC). Circular RNA_515 may serve as a novel prognostic biomarker for NSCLC cells whose upregulation enhanced growth and invasiveness of cancer cells through sponging miR‐296‐5p and activating RNF44.