Circ_PIP5K1A regulates cisplatin resistance and malignant progression in non-small cell lung cancer cells and xenograft murine model via depending on miR-493-5p/ROCK1 axis

Abstract

Background Chemoresistance limits the therapeutic effect of cisplatin (DDP) on non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) function as important regulators in chemoresistance. This study aimed to explore the regulation of circRNA Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Alpha (circ_PIP5K1A) in DDP resistance. Methods The expression analysis of circ_PIP5K1A, micoRNA-493-5p (miR-493-5p) and Rho Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1) was conducted through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell sensitivity was determined using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell proliferation and cell viability were evaluated by colony formation assay and MTT assay, respectively. Cell cycle and apoptosis detection was performed via flow cytometry. Cell motility was examined by transwell migration or invasion assay. Dual-luciferase reporter assay was applied to confirm the target binding. ROCK1 protein level was assayed via Western blot. In vivo assay was carried out using xenograft model in mice. Results Circ_PIP5K1A level was abnormally increased in DDP-resistant NSCLC tissues and cells. Silencing circ_PIP5K1A reduced DDP resistance, proliferation, cell cycle progression and cell motility in DDP-resistant NSCLC cells. Circ_PIP5K1A directly interacted with miR-493-5p in NSCLC cells. The function of circ_PIP5K1A was dependent on the negative regulation of miR-493-5p. MiR-493-5p directly targeted ROCK1 and circ_PIP5K1A regulated the ROCK1 level via acting as a sponge of miR-493-5p. Overexpression of miR-493-5p inhibited chemoresistance and cancer progression by downregulating ROCK1 expression in DDP-resistant NSCLC cells. Circ_PIP5K1A regulated DDP sensitivity in vivo via the miR-493-5p/ROCK1 axis. Conclusion These findings suggested that circ_PIP5K1A upregulated the ROCK1 expression to promote DDP resistance and cancer progression in NSCLC by sponging miR-493-5p.

MiR-493-5p alleviates lipopolysaccharide-induced inflammation in ATDC5 chondrogenic cells by targeting TAB2

“…Recently, it has been shown that miR-493-5p regulates the progression of several diseases, especially cancer. It was shown that miR-493-5p/ROCK1 affects malignant progression and cisplatin resistance of non-small cell lung cancer cells via circ_PIP5K1A in a xenograft murine model [12]. However, there has only been one study on the role of miR-493-5p in OA.…”

Integrative analysis of circulating microRNAs and the placental transcriptome in recurrent pregnancy loss

“…MiR-493-5p inhibits glioma progression by decreasing E2F3-mediated P53 and PI3K/AKT pathway dysfunction (Liu H. et al, 2022). Some studies have shown that mir-493-5p overexpression plays a negative regulatory role in esophageal cancer, osteosarcoma, cervical cancer, nonsmall cell lung cancer, and other malignancies by inhibiting cell proliferation/ migration/invasion (Feng et al, 2021;Wang et al, 2021;Liu Q. et al, 2022;Huang et al, 2022). Downregulation of miR-1285-3p reversed the effects of weak expression of circRNA_400029 on the progression and apoptosis of cervical cancer cells (Ma et al, 2022).…”

Differential expression profiles of miRNA in the serum of sarcopenic rats

“…Among the 14 miRNAs identified here, rno-miR-493-5p is reported to be associated with cancer cells [ [32] , [33] , [34] ]. In addition, our KEGG pathway analysis also indicated that miRNA21, 1, 34a, 34c, 133, 133a, and Let-7c also take part in the cancer pathway ( Fig.…”