|ZFIN ID: ZDB-PUB-171102-9|
The zebrafish miR-125c is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations and embryogenesis.
He, Y., Huang, C.X., Chen, N., Wu, M., Huang, Y., Liu, H., Tang, R., Wang, W.M., Wang, H.L.
|Source:||Oncotarget 8: 73846-73859 (Journal)|
|Registered Authors:||He, Yan|
|Keywords:||cdc25a, cell cycle, embryogenesis, hypoxia, miR-125c|
|PubMed:||29088751 Full text @ Oncotarget|
He, Y., Huang, C.X., Chen, N., Wu, M., Huang, Y., Liu, H., Tang, R., Wang, W.M., Wang, H.L. (2017) The zebrafish miR-125c is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations and embryogenesis.. Oncotarget. 8:73846-73859.
ABSTRACTHypoxia is a unique environmental stress. Hypoxia inducible factor-lα (HIF-lα) is a major transcriptional regulator of cellular adaptations to hypoxic stress. MicroRNAs (miRNAs) as posttranscriptional gene expression regulators occupy a crucial role in cell survival under low-oxygen environment. Previous evidences suggested that miR-125c is involved in hypoxia adaptation, but its precise biological roles and the regulatory mechanism underlying hypoxic responses remain unknown. The present study showed that zebrafish miR-125c is upregulated by hypoxia in a Hif-lα-mediated manner in vitro and in vivo. Dual-luciferase assay revealed that cdc25a is a novel target of miR-125c. An inverse correlation between miR-125c and cdc25a was further confirmed in vivo, suggesting miR-125c as a crucial physiological inhibitor of cdc25a which responds to cellular hypoxia. Overexpression of miR-125c suppressed cell proliferation, led to cell cycle arrest at the G1 phase in ZF4 cells and induced apoptotic responses during embryo development. More importantly, miR-125c overexpression resulted in severe malformation and reduction of motility during zebrafish embryonic development. Taken together, we conclude that miR-125c plays a pivotal role in cellular adaptations to hypoxic stress at least in part through the Hif-1α/miR-125c/cdc25a signaling and has great impact on zebrafish early embryonic development.
- Genes / Markers (8)