The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations.
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 postfertilization 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.
*Key Laboratory of Freshwater Animal Breeding and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, Wuhan, Hubei, China; and Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, Hubei, China.
Chun-Xiao
CX
Huang
*Key Laboratory of Freshwater Animal Breeding and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, Wuhan, Hubei, China; and Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, Hubei, China.
Nan
N
Chen
*Key Laboratory of Freshwater Animal Breeding and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, Wuhan, Hubei, China; and Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, Hubei, China.
Xin-Jie
XJ
Wu
*Key Laboratory of Freshwater Animal Breeding and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, Wuhan, Hubei, China; and Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, Hubei, China.
Cui-Hong
CH
Huang
*Key Laboratory of Freshwater Animal Breeding and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, Wuhan, Hubei, China; and Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, Hubei, China.
Yan
Y
He
*Key Laboratory of Freshwater Animal Breeding and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, Wuhan, Hubei, China; and Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, Hubei, China.
Rong
R
Tang
*Key Laboratory of Freshwater Animal Breeding and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, Wuhan, Hubei, China; and Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, Hubei, China.
Wei-Min
WM
Wang
*Key Laboratory of Freshwater Animal Breeding and Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, Wuhan, Hubei, China; and Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, Hubei, China hbauwhl@hotmail.com.
Huan-Ling
HL
Wang
D000222:Adaptation, Physiological; D000818:Animals; D002460:Cell Line; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D015854:Up-Regulation / Q000502:physiology; D015027:Zebrafish
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs
cell survival; embryonic development; hypoxamir; low oxygen