Circular RNA hsa_circ_0011298 enhances Taxol resistance of non‐small cell lung cancer by regulating miR‐486‐3p/CRABP2 axis

Abstract

Background: Circular RNAs (circRNAs) serve as critical regulators in the chemoresistance of human cancers, including non-small cell lung cancer (NSCLC). We aimed to explore the role of hsa_circ_0011298 (circ_0011298) and its mechanism in Taxol resistance of NSCLC. : Circ_0011298, microRNA-486-3p (miR-486-3p), and CRABP2 mRNA expression were determined using qRT-PCR. EdU and MTT assays were used to detect cell proliferation. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Cell migratory and invasive abilities were detected using transwell assay. Cellular glycolysis was determined by specific kits. Protein levels were examined by western blot. Dual-luciferase reporter and RIP assays were performed to confirm the relationship between miR-486-3p and circ_0011298 or CRABP2. Xenograft mice model was established to confirm the function of circ_0011298 in vivo. Results: Circ_0011298 was overexpressed in Taxol-resistant NSCLC cells and tissues. Circ_0011298 knockdown enhanced Taxol sensitivity by decreasing cell proliferation, migration, invasion, and glycolysis and inducing apoptosis and cell cycle arrest in Taxolresistant NSCLC cells. Circ_0011298 was a sponge of miR-486-3p, and the impact of circ_0011298 silencing on Taxol resistance was rescued by miR-486-3p inhibition. Moreover, miR-486-3p directly targeted CRABP2, and miR-486-3p inhibited Taxol resistance by targeting CRABP2. Furthermore, circ_0011298 regulated CRABP2 expression through targeting miR-486-3p. Importantly, circ_0011298 interference elevated Taxol sensitivity of NSCLC in vivo. Conclusion: Circ_0011298 elevated Taxol resistance of NSCLC by sponging miR-486-3p and upregulating CRABP2, providing a possible circRNA-targeted therapy for NSCLC. Methods

N6-methyladenosine modification of RanGAP1 promotes colorectal cancer progression via CRABP2

“…Using label-free quantitative proteomics (Label-free) technology and RNA-seq, we further explored the molecular mechanism downstream of RanGAP1 and identi ed CRABP2 as the downstream molecule. Previous studies have pointed to CRABP2 as a key proliferative agent in some cancers [30], and it is also closely associated with cancer metastasis by accelerating epithelial-mesenchymal transition [30][31][32][33][34][35][36]. However, its biological role in COAD has not been explored.…”

The significance of the crosstalk between ubiquitination or deubiquitination and ncRNAs in non-small cell lung cancer

“…The expression of circ_0008797 is low in NSCLC tissues and cell lines, which could attenuate proliferation, metastasis, and aerobic glycolysis by regulating miR-301a-3p/SOCS2 ( 66 ). The downregulation of circ_0011298 enhances the Taxol sensitivity of Taxol-resistant NSCLC cells by decreasing cell growth, metastasis, and glycolysis and promoting apoptosis and cell cycle arrest via the miR-486-3p/CRABP2 axis ( 67 ). In addition, circSLC25A16 and circPIP5K1A can induce hypoxia-inducible factor (HIF)-1a-dependent glycolysis by sponging miRNAs ( 68 , 69 ).…”

Allicin-Mediated Cell Cycle Regulation Reverses Taxol Resistance in NSCLC: Molecular Insights and Therapeutic Potentia

“…Cell Colony Formation Assay. A549/Taxol cells in the logarithmic growth phase were seeded in 6-well plates with 1.0 × 10 3 cells per well [1]. Te cells were treated with half of IC 10 , IC 10 , and twice IC 10 allicin for 24 h, and then the cells were replaced with drug-free medium and incubated for another 10 days.…”

“…Non-small cell lung cancer (NSCLC) is one of the most common cancers globally and has the highest mortality rate among all cancer types [1,2]. Taxol is a diterpene alkaloid chemical that is derived from natural sources and exhibits strong anticancer properties.…”