Circular RNA PRMT5 confers cisplatin-resistance via miR-4458/REV3L axis in non-small-cell lung cancer

Lung Cancer

Cell Biol Int. 2020 Aug 18. doi: 10.1002/cbin.11449. Online ahead of print.


Multi-factor and multi-step processes were elucidated to participate in the progression of non-small cell lung cancer (NSCLC). Circular RNA 0031250 (circ-PRMT5) was a vital factor in NSCLC. However, the role of circ-PRMT5 in cisplatin (DDP)-resistance needed to be further highlighted. Expression profiles of circ-PRMT5, microRNA (miR)-4458, and EV3-like DNA-directed polymerase ζ catalytic subunit (REV3L) were detected using quantitative real-time polymerase chain reaction (qRT-PCR).

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and transwell assays were performed to determine half maximal inhibitory concentration (IC50 ) of DDP, cell viability, apoptosis and invasion in vitro. Besides, the protein levels of REV3L and indicated proteins were examined through adopting western blot. Dual-luciferase reporter assay was performed to analyze the interaction between miR-4458 and circ-PRMT5 or REV3L. The function role of circ-PRMT5 was explored using xenograft tumor model. Levels of circ-PRMT5 and REV3L were markedly increased, while miR-4458 was downregulated in resistant tissues and cells. Knockdown of circ-PRMT5 enhanced cell apoptosis, DDP-sensitivity, and declined metastasis in NSCLC with DDP-resistance. Besides, miR-4458 inhibition or REV3L upregulation could revert circ-PRMT5 absence-mediated effect on DDP-sensitivity in vitro. Mechanically, circ-PRMT5 was a sponge of miR-4458 to regulate REV3L. Importantly, circ-PRMT5 silencing could interacted with DDP-treatment expedite the decrease of tumor growth in vivo. Circ-PRMT5 promoted DDP-resistance via REV3L by sponging miR-4458 in NSCLC, thus providing a novel therapeutic strategy for patients with NSCLC. This article is protected by copyright. All rights reserved.