Defective Homologous Recombination Repair By Up‐Regulating Lnc‐HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage

• DOI: 10.1002/advs.202207435
• Publication Date: 2024-01-30T02:33:46Z
• Authors: Weina Chen; Chenyang Mi; Ying Zhang; Yang Yang; Wenxin Huang; Zhongyan Xu; Jingsong Zhao; Rong Wang; Manli Wang; Shukun Wan; Xiaoqing Wang; Huidong Zhang
• Keywords: Trophoblast

Abstract Human trophoblast cells are crucial for healthy pregnancy. However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in may induce miscarriage is completely unknown. Moreover, abundance BRCA1 (a protein HR repair), its recruitment to DSB foci, and epigenetic regulatory mechanisms, also fully unexplored. In this work, it identified that a novel lnc‐HZ10, which highly experssed villous tissues recurrent (RM) vs their control group, suppresses cell. Lnc‐HZ10 AhR (aryl hydrocarbon receptor) form positive feedback loop. acts as transcription factor promote lnc‐HZ10 transcription. Meanwhile, increases levels by suppressing CUL4B‐mediated ubiquitination degradation. Subsequently, transcription; (mainly 1‐447 nt) interacts with γ‐H2AX; thus, impairs interactions BRCA1. BPDE exposure trigger loop suppress cells, possibly inducing miscarriage. Knockdown murine Ahr efficiently recovers placental alleviates mouse model. Therefore, suggested AhR/lnc‐HZ10/BRCA1 axis be promising target alleviation unexplained