title: Conserved miR-26b enhances ovarian granulosa cell apoptosis through HAS2-HA-CD44-Caspase-3 pathway by targeting HAS2.
abstract: The hyaluronan synthase 2 (HAS2)-hyaluronic acid (HA)-CD44-Caspase-3 pathway is involved in ovarian granulosa cell (GC) functions in mammals. HAS2 is a key enzyme required for HA synthesis and is the key factor in this pathway. However, the regulation of HAS2 and the HAS2-mediated pathway by microRNAs in GCs is poorly understood. Here, we report that miR-26b regulates porcine GC (pGC) apoptosis through the HAS2-HA-CD44-Caspase-3 pathway by binding directly to the 3'- untranslated region of HAS2 mRNA. Knockdown of miR-26b reduced pGC apoptosis. Luciferase reporter assays demonstrated that HAS2 is a direct target of miR-26b in pGCs. Knockdown and overexpression of miR-26b increased and decreased, respectively, HA content, and HAS2 and CD44 expression in pGCs. At the same time, inhibition and overexpression of miR-26b decreased and increased the expression of Caspase-3, a downstream factor in the HAS2-HA-CD44 pathway. Moreover, knockdown of HAS2 enhanced pGC apoptosis, reduced the inhibitory effects of a miR-26b inhibitor on pGC apoptosis, repressed HA content and CD44 expression, and promoted Caspase-3 expression. In addition, overexpression of HAS2 has a opposite effect. Collectively, miR-26b positively regulates pGC apoptosis via a novel HAS2-HA-CD44-Caspase-3 pathway by targeting the HAS2 gene.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Jiying
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Wang
authors.initials: W
authors.lastname: Yao
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Xie
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Zengxiang
authors.initials: Z
authors.lastname: Pan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D013552:Swine
chemical_list: D018960:Hyaluronan Receptors; D035683:MicroRNAs; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D053148:Caspase 3