Different Effects of LncRNA NDRG1-OT1_v4 Fragments on Regulating NDRG1 Transcription in Breast Cancer Cells Under Hypoxia

• Main Authors: Ching-Ching Yeh, 葉京青
• Other Authors: Liang-Chuan Lai
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/9n566s

碩士 === 國立臺灣大學 === 生理學研究所 === 106 === Hypoxia is a crucial factor in aggressiveness of solid tumor by driving multiple signaling pathways. Recent researchers indicated that long non-coding RNA (lncRNA) could promote or inhibit tumor aggressiveness by regulating gene expression. Previous studies in our laboratory found the expression of lncRNA NDRG1-OT1_v4 significantly increased under hypoxia by next-generation sequencing (NGS). Moreover, it was discovered that the NDRG1-OT1_v4 inhibited NDRG1 at both mRNA and protein levels of NDRG1. At the protein level, NDRG1-OT1_v4 improved NDRG1 degradation via ubiquitin-mediated proteolysis pathway. However, the repressive mechanism of NDRG1 at RNA level was still unknown. In this studies, we found that NDRG1-OT1_v4 decreased the NDRG1 promoter activities when we overexpressed NDRG1-OT1_v4 under hypoxia. The fragment (150-263 nt) of NDRG1-OT1_v4 repressed NDRG1 promoter activity significantly by increasing the binding affinity of hnRNPA1. On the other hand, another fragment (264-392 nt) of NDRG1-OT1_v4 improved NDRG1 promoter activity by recruiting HIF-1 alpha. In conclusion, we found a novel mechanism that different fragments of same lncRNA could cause opposite effects on the identical target gene.