The zebrafish miR-125c is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations and embryogenesis

// Yan He 1, 2, * , Chun-Xiao Huang 1, 2, * , Nan Chen 1, 2 , Meng Wu 1, 2 , Yan Huang 1, 2 , Hong Liu 1, 2 , Rong Tang 1, 2 , Wei-Min Wang 1 and Huan-Ling Wang 1, 2 1 Key Laboratory of Freshwater Animal Breeding, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, 430070, Wuhan, PR China 2 Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, 430070, Wuhan, PR China * These authors contributed equally to this work Correspondence to: Huan-Ling Wang, email: hbauwhl@hotmail.com Keywords: hypoxia, miR-125c, cdc25a, cell cycle, embryogenesis Received: February 09, 2017      Accepted: May 06, 2017      Published: May 18, 2017 ABSTRACT Hypoxia 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.