Upregulation of microRNA-25-3p inhibits proliferation, migration and invasion of osteosarcoma cells in vitro by directly targeting SOX4

Abstract

Osteosarcoma (OS) is among the most common primary tumors of bone tissue, and occurs primarily in children and young adults. Despite the development of novel therapeutic approaches, the prognosis of OS remains poor. MicroRNAs (miRNAs) are involved in the development and progression of various types of human cancer and may have potential as novel therapeutic targets for cancer treatment. The present study aimed to investigate the expression and biological functions of miRNA‑25‑3p in OS, and explore the molecular mechanisms underlying its actions. In the present study, miRNA‑25‑3p was detected in OS tissues and cell lines. The functional roles of miRNA‑25‑3p in OS cells were evaluated using a Cell Counting Kit 8 assay and cellular migration and invasion assays. The molecular mechanisms underlying the tumor‑suppressing roles of miRNA‑25‑3p in OS were explored using bioinformatics analysis, luciferase reporter assay, western blotting and the reverse transcription‑quantitative polymerase chain reaction. The expression of miRNA‑25‑3p was revealed to be downregulated in OS tissues and cell lines compared with non‑tumor bone tissues and normal osteoblasts, respectively. miRNA‑25‑3p overexpression was demonstrated to significantly suppress the proliferation, migration and invasion of OS cells in vitro. In addition, sex‑determining region‑related high mobility group box (SOX) 4 was identified as a direct target gene of miRNA‑25‑3p, and was further investigated. Similarly to miRNA‑25‑3p overexpression, SOX4 knockdown was demonstrated to suppress OS cell proliferation, migration and invasion. Furthermore, SOX4 expression was revealed to be significantly upregulated in OS tissues compared with in adjacent non‑tumor bone tissues, and Spearman's correlation analysis indicated a negative correlation between SOX4 mRNA and miRNA‑25‑3p expression levels in OS tissues. The present findings suggested that miRNA‑25‑3p may act as a tumor suppressor by targeting SOX4 expression in bone tissue. Therefore, miRNA‑25‑3p may have potential as a novel therapeutic target for the treatment of patients with OS.

Long Non-Coding RNA TUG1 Promotes Proliferation and Inhibits Apoptosis of Osteosarcoma Cells by Sponging miR-132-3p and Upregulating SOX4 Expression

“… 16 26 27 For example, SOX4, as a target of microRNA-212 and microRNA-25-3p together with miR-132, could weaken these miRNAs-mediated inhibition effects on progression of OS cells. 16 18 19 Consequently, we further demonstrated that SOX4 was a target gene of miR-132-3p by bioinformatics analysis, luciferase reporter assays, and western blot assays, the results of which were consistent with those in a previous study. 16 Additionally, miR-132-3p repressed proliferation and induced apoptosis of OS cells, while this effect of miR-132-3p was partly abrogated by SOX4 overexpression.…”

“…Among candidate genes, SOX4 has been identified as an oncogene in OS ( Fig. 3A ), 16 18 19 and was chosen for further study. To validate whether the putative binding sites of SOX4-3'UTR and miR-132-3p are important for the interaction between miR-132-3p and SOX4, dual luciferase reporter assays and mutation assays were performed.…”

miR‑188 suppresses tumor progression by targeting SOX4 in pediatric osteosarcoma

“…We predicted the target gene of miR-188 by using the TargetScan and PicTar algorithm software and found that SOX4 is a potential target of miR-188. SOX4 is a key oncogene in OS development (20,21). Therefore, we chose SOX4 for further investigation.…”

“…An abnormal SOX4 overexpression is often linked to tumorigenicity and cancer stemness (30). SOX4 is upregulated in various cancers, such as ovarian cancer (29), renal cell carcinoma (31), lung adenocarcinoma (32), gastric carcinoma (33), and OS (34). Previous studies showed that SOX4 is regulated by miRNAs in OS and involved in the promotion of OS progression.…”

miR-25 Promotes Melanoma Progression by regulating RNA binding motif protein 47

“…Previous studies have demonstrated that miR-25 promotes cancer cell proliferation, migration and invasion by regulating the expression of various protein in tumor-associated signaling pathways [10][11][12][13]. However, another study demonstrated that miR-25 suppresses cell growth and mobility of osteosarcoma via targeting SOX4 [14]. In addition, other studies have shown that miR-25 inhibits cell apoptosis in various cancers, including gastric adenocarcinoma, lung cancer and pancreatic cancer [15][16][17][18].…”