Expression and function of microRNA-497 in human osteosarcoma

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.

Section: Upregulation Of Microrna-25-3p Inhibits Proliferation Migramentioning

confidence: 99%

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

Zhou

Yue

et al. 2017

“…Low miR-497 expression may be a predictor of poor prognosis. Furthermore, miR-497 is expressed at low levels in non-small cell lung cancer ( 35 ), prostate cancer ( 36 ), pancreatic cancer ( 37 ), ovarian cancer ( 38 ), bladder cancer ( 39 ) and osteosarcoma ( 40 ). These findings suggested that miR-497 is frequently lowly expressed in human cancer and could be a therapeutic marker for its diagnosis and prognosis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-497 inhibits cellular proliferation, migration and invasion of papillary thyroid cancer by directly targeting AKT3

Zhuang

Wang

et al. 2017

Thyroid cancer is the most common tumor of the endocrine organs. Emerging studies have indicated the critical roles of microRNAs (miRs) in papillary thyroid cancer (PTC) formation and progression through function as tumor suppressors or oncogenes. The present study investigated the expression level and biological roles of miR-497 in PTC and its underlying mechanisms. It was demonstrated that the expression level of miR-497 was reduced in both PTC tissues and cell lines. Enforced expression of miR-497 suppressed PTC cell proliferation, migration and invasion. According to bioinformatics analysis, a luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blotting, RAC-γ serine/threonine-protein kinase (AKT3) was demonstrated to be the direct target gene of miR-497. In addition, AKT3 expression increased in PTC tissues and negatively correlated with miR-497 expression. Furthermore, downregulation of AKT3 also suppressed cell proliferation, migration and invasion of PTC, which had similar roles to miR-497 overexpression in PTC cells. Taken together, these results suggested that this newly identified miR-497/AKT3 signaling pathway may contribute to PTC occurrence and progression. These findings provide novel potential therapeutic targets for the therapy of PTC.

“…IGF-1R, a tyrosine kinase receptor, contains two extracellular α subunits with a ligand-binding site, two transmembrane β subunits and intracellular tyrosine kinase activity (29). It has previously been demonstrated that IGF-1R is involved in IGF-I and IGF-II signaling, and therefore regulates cell proliferation, cell cycle, apoptosis, metastasis, survival and differentiation (30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-186 targets IGF-1R and exerts tumor-suppressing functions in glioma

Jiang

Wang

Fang

et al. 2017

Glioma is the most common malignant brain tumor in adults and represents one of the most aggressive and life‑threatening types of cancer in humans. Increasing studies have revealed that microRNAs are abnormally expressed in various types of human cancer, and have oncogenic or tumor suppressive roles, which depend primarily on the type of cancer. The present study aimed to investigate the expression level and effects of microRNA‑186 (miR‑186) on glioma, and its underlying molecular mechanism. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis was performed to detect the expression of miR‑186 in glioma tissues and cell lines. Cell proliferation and invasion were assessed using MTT and cell invasion assays, respectively. Bioinformatics analysis and a luciferase reporter assay were performed to identify insulin‑like growth factor 1 receptor (IGF‑1R) as a novel target gene of miR‑186. The mRNA expression level of IGF‑1R was also measured using RT‑qPCR analysis. The association between miR‑186 and the expression of IGF‑1R was evaluated using Spearman's correlation anal-ysis. Furthermore, the regulatory effects of miR‑186 on the mRNA and protein expression of IGF‑1R were determined using RT‑qPCR and western blot analyses. Finally, the biological effects of the underexpression IGF‑1R on glioma cells were investigated. The results showed that miR‑186 was significantly downregulated in glioma tissues and cell lines. Inducing the expression of miR‑186 suppressed glioma cell proliferation and invasion. IGF‑1R was confirmed as a direct target gene of miR‑186. In addition, the mRNA expression of IGF‑1R was upregulated and inversely correlated with that of miR‑186 in glioma tissues. The effects of IGF‑1R‑knockdown on glioma cell proliferation and invasion were similar to the effects induced by the overexpression of miR‑186. These findings demonstrated that miR‑186 acted as a tumor suppressor by targeting IGF‑1R in glioma, suggesting miR‑186 may be a potential therapeutic target for the treatment of this disease.