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MiR-4295 promotes cell proliferation, migration and invasion of osteosarcoma through targeting interferon regulatory factor 1

ABSTRACT: Osteosarcoma (OS) is the most common form of primary malignant bone tumor. Despite encouraging progress in the treatment of OS, the survival rate for patients with OS has remained unchanged over the past 40 years. It has been established that miRNA plays a crucial regulatory role in the progression and development of OS. To explore the potential association of miRNAs with OS, bioinformatics techniques were used to screen for differentially expressed miRNA genes in OS in the Gene Expression Omnibus database. In the GSE70367 database, it was revealed that miR-4295 expression was abnormally elevated in the expression of OS cells. To characterize the potential function of miR-4295 in OS, the expression levels of miR-4295 in 30 samples of OS and adjacent normal tissues was examined. The results revealed that the expression of miR-4295 was significantly increased in OS tissues compared with the paired normal tissues. Moreover, the expression levels of miR-4295 in OS cell lines (MG-63 and Saos-2) were significantly higher compared with those in the normal human mesenchymal stem cells. In addition, miR-4295 was associated with OS cell proliferation, migration and invasion. Furthermore, it was demonstrated that the expression of interferon regulatory factor (IRF)1, a tumor suppressor, was regulated by miR-4295 directly in OS cells. Taken together, the present results revealed that miR-4295 may act as a tumor activator by targeting IRF1 during the progression of OS. Investigating miR-4295 may provide novel insight into the mechanisms of OS metastasis, and inhibition and targeting miR-4295 may be a novel therapeutic strategy for the treatment of OS.

SUBMITTER: Cheng J

PROVIDER: S-EPMC7517570 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Project description:The authors' previous study revealed that the serum levels of microRNA (miR)-663b are significantly increased in patients with nasopharyngeal carcinoma (NPC), and are associated with NPC progression and poor prognosis. However, the molecular mechanism of underlying NPC growth and metastasis remains unclear. In the present study, quantitative polymerase chain reaction and western blot analyses were performed to examine changes to mRNA and protein expression, respectively. MTT, wound healing and Transwell assays were used to examine cell proliferation, migration and invasion, respectively. Luciferase reporter gene assays were performed to identify target genes of miR-663b. It was demonstrated that miR-663b was significantly upregulated in NPC tissue compared with non-tumor nasopharyngeal epithelial tissue samples. Furthermore, miR-663b expression gradually increased with advancing stages of NPC, with the highest expression being observed in the latest stage IV. The increased expression of miR-663b was associated with advanced clinical stage and lymph node metastasis. In addition, miR-663b expression was increased in NPC cell lines compared with normal nasopharyngeal epithelial NP69 cells. Knockdown of miR-663b resulted in a significant reduction in the proliferation, migration and invasion of NPC CNE1 cells. Tumor suppressor candidate 2 (TUSC2) was identified as a novel target gene of miR-663b. It was further demonstrated that TUSC2 was significantly downregulated in NPC tissue samples and cell lines. miR-663b negatively regulated the expression of TUSC2 at the post-transcriptional level in CNE1 cells. Additionally, inhibition of TUSC2 expression attenuated the suppressive effects of miR-663b downregulation on the proliferation, migration and invasion of CNE1 cells. To the best of our knowledge, this is the first study to demonstrate that miR-663b, which is upregulated in NPC, promotes the proliferation, migration and invasion of NPC cells, partially through the inhibition of TUSC2 expression. Therefore, it is suggested that miR-663b is a promising therapeutic target for the treatment of patients with NPC.

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MiR-4295 promotes cell proliferation, migration and invasion of osteosarcoma through targeting interferon regulatory factor 1

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