1. miR-422a inhibits osteosarcoma proliferation by targeting BCL2L2 and KRAS.
- Author
-
Zhang H, He QY, Wang GC, Tong DK, Wang RK, Ding WB, Li C, Wei Q, Ding C, Liu PZ, Cui HC, Zhang X, Li D, Tang H, and Ji F
- Subjects
- Apoptosis Regulatory Proteins genetics, Bone Neoplasms genetics, Bone Neoplasms pathology, Cell Line, Female, Humans, Male, MicroRNAs genetics, Osteosarcoma genetics, Osteosarcoma pathology, Protein Biosynthesis, Proto-Oncogene Proteins p21(ras) genetics, RNA, Neoplasm genetics, Apoptosis, Apoptosis Regulatory Proteins biosynthesis, Bone Neoplasms metabolism, Cell Proliferation, Genes, Tumor Suppressor, MicroRNAs metabolism, Osteosarcoma metabolism, Proto-Oncogene Proteins p21(ras) biosynthesis, RNA, Neoplasm metabolism
- Abstract
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. However, the underlying mechanism of osteosarcoma carcinogenesis and progression remains unknown. In the present study, we evaluated the expression profile of miRNAs in osteosarcoma tissues and the adjacent normal tissues. We found that the expression of miR-422a was down-regulated in osteosarcoma tissues and cell lines. In addition, we observed significantly elevated levels of repressive H3K9me3 and H3K27me3 and decreased active H3K4me3 on the promote region of miR-422a in osteosarcoma cells and clinical samples. Furthermore, up-regulation of miR-422a exhibited both in vitro and in vivo anti-tumor effects by inhibiting osteosarcoma cell growth and inducing apoptosis and cell cycle arrest. We also found that miR-422a targeted BCL2L2 and KRAS and negatively regulated their protein expression. Furthermore, restoration of miR-422a and knockdown of BCL2L2 and KRAS promoted apoptosis and induce cell cycle arrest in osteosarcoma cells. Taken together, the present study demonstrates that miR-422a may serve as a tumor suppressor in osteosarcoma via inhibiting BCL2L2 and KRAS translation both in vitro and in vivo Therefore, miR-422a could be developed as a novel therapeutic target in osteosarcoma., (© 2018 The Author(s).)
- Published
- 2018
- Full Text
- View/download PDF