Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a high fatality rate in men and women worldwide. Recently, microRNAs (miRNAs) have been reported to be diagnostic biomarkers and therapeutic targets in NSCLC. MiR-223-3p was proved to act as a promoter in NSCLC progression. However, the regulatory mechanism of miR-223-3p in NSCLC remains little known. This study aimed to explore the regulatory mechanism between miR-223-3p and its target gene Ras homolog family member B (RHOB) in NSCLC. The mRNA level of miR-223-3p and RHOB was measured by quantitative reverse transcription PCR. Furthermore, cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry was conducted to analyze cell apoptosis. Transwell assays and wound healing assay were employed to examine migration and invasion. The target relationship between miR-223-3p and RHOB was predicted by starBase online database and verified by dual-luciferase assay. The protein level of RHOB was tested by western blot. Our data suggested that miR-223-3p was upregulated in NSCLC tissues and cell lines and high level of miR-223-3p contributed to a poor survival in NSCLC patients. Knockdown of miR-223-3p exerted inhibitory effects on NSCLC cell viability, migration, and invasion and promotion effect on cell apoptosis. Furthermore, RHOB was directly targeted by miR-223-3p and constrained NSCLC progression. Moreover, knockdown of RHOB rescued the effect of anti-miR-223-3p on NSCLC progression. In vivo experiments indicated that miR-223-3p deletion suppressed tumor growth. MiR-223-3p could regulate the NSCLC cellular processes through targeting RHOB.
Highlights
Lung cancer is one of the most common cancers with a high fatality rate worldwide [1,2]
To further elucidate the role of miR-223-3p in non-small cell lung cancer (NSCLC), SKMES-1 and H1299 cells were transfected with anti-negative control (NC) or antimiR-223-3p for 48 h
MiRNAs were proved to participate in the progression of various cancers, including NSCLC
Summary
Lung cancer is one of the most common cancers with a high fatality rate worldwide [1,2]. MicroRNAs (miRNAs) are a class of small noncoding RNAs with a length of about 22 nt and negatively regulate the gene expression by binding to the 3′-untranslated region (3′-UTR) of target mRNAs [7]. Many studies have indicated that miRNAs played important roles in various human cancers [8]. MiR-223-3p, located on Xq12, was reported to be involved in the regulation of several cancers. MiR-223-3p expression was associated with a high risk for progression in adenocarcinoma patients [9]. A previous study indicated that miR-223-3p could inhibit cancer cell aggressiveness by targeting genes involving in bladder cancer pathogenesis [10]. MiR-223-3p was found to be significantly upregulated and might be a diagnostic biomarker and therapeutic target in
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