PUBLICATION

The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations

Authors
Huang, C.X., Chen, N., Wu, X.J., Huang, C.H., He, Y., Tang, R., Wang, W.M., Wang, H.L.
ID
ZDB-PUB-150813-7
Date
2015
Source
FASEB journal : official publication of the Federation of American Societies for Experimental Biology   29(12): 4901-13 (Journal)
Registered Authors
Keywords
cell survival, embryonic development, hypoxamir, low oxygen
MeSH Terms
  • Adaptation, Physiological*
  • Animals
  • Cell Line
  • Humans
  • Hypoxia/genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit/physiology*
  • MicroRNAs/genetics*
  • Multigene Family
  • Up-Regulation/physiology
  • Zebrafish
PubMed
26265472 Full text @ FASEB J.
Abstract
Hypoxia, a unique and essential environmental stress, evokes highly coordinated cellular responses, and hypoxia-inducible factor (HIF) 1 in the hypoxia signaling pathway, an evolutionarily conserved cellular signaling pathway, acts as a master regulator of the transcriptional response to hypoxic stress. MicroRNAs (miRNAs), a major class of posttranscriptional gene expression regulators, also play pivotal roles in orchestrating hypoxia-mediated cellular adaptations. Here, global miRNA expression profiling and quantitative real-time PCR indicated that the up-regulation of the miR-462/miR-731 cluster in zebrafish larvae is induced by hypoxia. It was further validated that miR-462 and miR-731 are up-regulated in a Hif-1α-mediated manner under hypoxia and specifically target ddx5 and ppm1da, respectively. Overexpression of miR-462 and miR-731 represses cell proliferation through blocking cell cycle progress of DNA replication, and induces apoptosis. In situ detection revealed that the miR-462/miR-731 cluster is highly expressed in a consistent and ubiquitous manner throughout the early developmental stages. Additionally, the transcripts become restricted to the notochord, pharyngeal arch, liver, and gut regions from postfertiliztion d 3 to 5. These data highlight a previously unidentified role of the miR-462/miR-731 cluster as a crucial signaling mediator for hypoxia-mediated cellular adaptations and provide some insights into the potential function of the cluster during embryonic development.-Huang, C.-X., Chen, N., Wu, X.-J., Huang, C.-H., He, Y., Tang, R., Wang, W.-M., Wang, H.-L. The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations.
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