1. miR-29a-3p mitigates the development of osteosarcoma through modulating IGF1 mediated PI3k/Akt/FOXO3 pathway by activating autophagy.
- Author
-
Qi S, Xu L, Han Y, Chen H, and Cheng A
- Subjects
- Adolescent, Autophagy genetics, Cell Line, Tumor, Cell Movement, Cell Proliferation, Child, Forkhead Box Protein O3 metabolism, Gene Expression Regulation, Neoplastic genetics, Humans, Insulin-Like Growth Factor I genetics, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Bone Neoplasms pathology, Insulin-Like Growth Factor I metabolism, MicroRNAs genetics, MicroRNAs metabolism, Osteosarcoma pathology
- Abstract
Osteosarcoma (OS), occurring in mesenchymal tissues and with a high degree of malignancy, is most common in children and adolescents. At present, we intend to figure out the expression and functions of miR-29a-3p in OS development. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to monitor the expression of miR-29a-3p and IGF1 in OS tissues and adjacent non-tumor tissues. Then, the 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, colony formation experiment, western blot and Transwell assay were conducted to validate OS cell proliferation, colony formation ability, apoptosis, migration and invasion. Next, the association between miR-29a-3p and IGF1 was corroborated by the dual-luciferase reporter assay and the Pearson correlation analysis. Finally, WB was implemented to test the levels of autophagy-related proteins LC3-I/LC3-II, Beclin-1, p62, and the IGF-1 R/PI3k/Akt/FOXO3 axis in OS cells. As a result, miR-29a-3p was down-regulated in OS tissues (versus adjacent non-tumor tissues) and OS cell lines. Overexpressing miR-29a-3p aggravated apoptosis, dampened cell proliferation, colony formation, migration and invasion, and promoted autophagy of OS cells. IGF1 was identified as a target of miR-29a-3p. IGF1 induced oncogenic effects in OS by activating IGF-1 R/ PI3k/Akt pathway, and it dampened the tumor-suppressive effect of miR-29a-3p on OS. Taken together, miR-29a-3p repressed the OS evolvement through inducing autophagy and inhibiting IGF1 mediated PI3k/Akt/FOXO3 pathway.
- Published
- 2022
- Full Text
- View/download PDF