Circ_0001821 knockdown suppresses growth, metastasis, and TAX resistance of non‐small‐cell lung cancer cells by regulating the miR‐526b‐5p/GRK5 axis

Abstract

Abstract Non‐small‐cell lung cancer (NSCLC) remains a huge obstacle to human health. Certain circular RNAs endow with crucial regulatory roles in NSCLC progression. Here, we investigated the functional effects of circ_0001821 on cellular behaviors of NSCLC cells and explored the possible mechanism. The expression of circ_0001821, microRNA (miR)‐526b‐5p, and G protein‐coupled receptor kinase 5 (GRK5) was determined by quantitative real‐time polymerase chain reaction or Western blot assay. Clonogenicity in NSCLC cells was detected via colony formation assay. Cell migration and invasion were monitored by Transwell assay. Cell sensitivity to paclitaxel (TAX) evaluated by Cell Counting Kit‐8 assay. Cell apoptosis was assessed by flow cytometry, caspase‐3 activity, and caspase‐9 activity. The targeted relationship between miR‐526b‐5p and circ_0001821 or GRK5 was confirmed by dual‐luciferase reporter or RNA pull‐down assay. Moreover, the role of circ_0001821 in vivo was examined by xenograft model assay. The results presented that the expression of circ_0001821 and GRK5 was increased, while miR‐526b‐5p expression was decreased in NSCLC tissues and cells. Circ_0001821 knockdown reduced colony formation ability and metastasis ability but enhanced TAX sensibility and apoptosis of NSCLC cells, which was attenuated by miR‐526b‐5p inhibition or GRK5 overexpression. Circ_0001821 targeted miR‐526b‐5p, and miR‐526b‐5p targeted GRK5. Circ_0001821 could upregulate GRK5 expression by sponging miR‐526b‐5p. Depletion of circ_0001821 also blocked tumor growth in vivo. In conclusion, the depletion of circ_0001821 inhibited NSCLC progression, at least in part, by modulating the miR‐526b‐5p/GRK5 axis.

Keywords

• circ_0001821
• GRK5
• miR‐526b‐5p
• NSCLC
• TAX resistance
• TAX sensibility