Circular RNA NOX4 promotes the development of colorectal cancer via the microRNA‑485‑5p/CKS1B axis

Abstract

Colorectal cancer (CRC) is a common malignancy globally. The aim of the present study was to explore the role and the working mechanism of circular RNA NADPH oxidase 4 (circNOX4; circBase ID, hsa_circ_0023990) in CRC. Reverse transcription-quantitative (RT-q)PCR was used to examine the expression of circNOX4, NOX4 mRNA and microRNA (miR)-485-5p in CRC tissues and cell lines. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays were performed to analyze CRC cell viability and motility. The glycolytic ability of CRC cells was assessed by measuring glucose consumption, lactate production, extracellular acidification and O 2 consumption rates using commercial kits. The starBase database was used to predict the targets of circNOX4 and miR-485-5p, and the interaction was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. A murine xenograft model was established to verify the role of circNOX4 in CRC in vivo. The results demonstrated that the expression of circNOX4 was upregulated in CRC tissues and cell lines compared with that in adjacent normal tissues and a normal colon epithelial cell line, respectively. The expression of circNOX4 was negatively associated with the prognosis of patients with CRC. CircNOX4 silencing suppressed the proliferation, migration, invasion and glycolysis of CRC cells. miR-485-5p was identified as a target of circNOX4. CircNOX4 promoted CRC progression by sponging miR-485-5p. miR-485-5p was demonstrated to bind to the 3' untranslated region (UTR) of CDC28 protein kinase regulatory subunit 1B (CKS1B). miR-485-5p overexpression-mediated malignant properties of CRC cells were partly reversed by the transfection with the CKS1B overexpression plasmid. CircNOX4 silencing restrained the CRC xenograft growth in vivo. Collectively, the results of the present study demonstrated that circNOX4 may serve an oncogenic role in CRC by promoting the proliferation, migration, invasion and glycolysis of CRC cells via the miR-485-5p/CKS1B axis.

CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR‐485‐5p/SLC38A1 axis

“…Liu et al disclosed that miR‐485‐5p restrained CRC cell proliferation and motility as well as stimulated apoptosis through circAPLP2/miR‐485‐5p/FOXK1 regulatory axis 18 . Wang et al demonstrated the inhibitory effects of miR‐485‐5p on CRC by circNOX4/miR‐485‐5p/CKS1B axis 41 . In line with these findings, we found that miR‐485‐5p elevation caused a remarkable suppression in CRC cell colony formation and motility and a distinct enhancement in cell apoptosis.…”

A Pan-Cancer Analysis of Clinical Prognosis and Immune Infiltration of CKS1B in Human Tumors

“…Liu et al reported CKS1B in breast cancer was associated with patient's age, estrogen, and progesterone receptor levels and increased with malignant degree [ 15 ]. Besides, CKS1B was also found to be upregulated in patients with prostate cancer, colorectal cancer, leukemia, retinoblastoma, and other malignant diseases or animal models [ 10 , 28 , 29 ]. Therefore, CKS1B is generally regarded as a cancer-promoting factor.…”

Circular RNA circ-LARP1B contributes to cutaneous squamous cell carcinoma progression by targeting microRNA-515-5p/TPX2 microtubule nucleation factor axis

“…MTT assay was conducted as previously described [ 21 ]. In brief, a total of 20 μL of 5% MTT reagent (SenBeJia Biological Technology, Jiangsu, China) was incubated with CSCC cells for 4 h. The formazan products were dissolved with 100 μL of dimethyl sulfoxide (DMSO; Sangon Biotech, Shanghai, China).…”

“…Transwell invasion assay was conducted as previously described [ 21 ]. The diluted Matrigel (50 μL/well; BD Biosciences, San Jose, CA, USA) was added to the upper compartments.…”