miR-29a-3p mitigates the development of osteosarcoma through modulating IGF1 mediated PI3k/Akt/FOXO3 pathway by activating autophagy

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.

KEYWORDS:

• miR-29a-3p
• IGF1
• osteosarcoma
• progression
• signaling pathway

Authors contribution

Conceived and designed the experiments: Qi Song, Li Xu, Hongkun Chen;

Performed the experiments: Qi Song, Li Xu, Yongyuan Han, Yongyuan Han;

Statistical analysis: Qi Song, Li Xu, Yongyuan Han;

Wrote the paper: Qi Song, Hongkun Chen, Anyuan Cheng.

All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics statement

Our study was approved by the Ethics Review Board of Wuhan No 1 Hospital.

Data availability

The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not- for- profit sectors.