Circ_0058608 contributes to the progression and taxol resistance of non-small cell lung cancer by sponging miR-1299 to upregulate GBP1

Abstract

Circular RNAs (circRNAs) act as key regulators in human cancers and chemoresistance. Here, we aimed to explore the role and mechanism of circ_0058608 in nonsmall cell lung cancer (NSCLC) and taxol resistance. The expression of circ_0058608, microRNA-1299 (miR-1299) and guanylate binding protein 1 (GBP1) mRNA was determined by quantitative real-time PCR. In-vitro and in-vivo assays were conducted using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), colony formation, transwell assays, flow cytometry and animal xenograft experiments. The interaction between miR-1299 and circ_0058608 or GBP1 was confirmed by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Circ_0058608 was overexpressed in NSCLC tissues/cells and taxol-resistant NSCLC tissues/ cells. Circ_0058608 knockdown inhibited NSCLC cell proliferation and metastasis and also suppressed tumor growth in vivo. Moreover, circ_0058608 knockdown increased taxol sensitivity by increasing taxol-induced apoptosis in taxol-resistant NSCLC cells. Moreover, circ_0058608 silencing enhanced taxol-induced tumor growth of NSCLC in vivo. MiR-1299 was a target of circ_0058608, and the effects of circ_0058608 knockdown on NSCLC cell progression and taxol resistance were reversed by miR-1299 inhibition. Additionally, miR-1299 could interact with GBP1, and miR-1299 suppressed NSCLC cell progression and taxol resistance by targeting GBP1. Furthermore, circ_0058608 could regulate GBP1 expression by sponging miR-1299. Circ_0058608 promoted the progression and taxol resistance of NSCLC by regulating the miR-1299/GBP1 axis.

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

“…MicroRNAs (miRNAs), small non-coding RNAs (18–24 nucleotides), regulate cancer initiation and progression [ 176 ], autophagy [ 177 ], and anti-cancer drug resistance [ 178 ]. miRNAs target multiple genes and play diverse roles.…”

Croton Alkaloids Suppresses Breast Cancer Cell Proliferation, Migration and Invasion through mediating Circular_0079593

“…By acting as a target of circ_0006404, miR-1299 repressed cell viability and metastasis in prostate cancer [30] . circ_0058608 contributed to lung cancer cell malignant progression and chemo resistance via absorbing miR-1299 [31] . Also, miR-1299 was down-regulated in BC and up-regulated miR-1299 expression inhibited BC progression [32] .…”