Adlat Salah, Sah Rajiv Kumar, Hayel Farooq, Chen Yang, Bah Fatoumata Binta, Al-Azab Mahmoud, Bahadar Noor, Myint May, Oo Zin Mar, Nasser M I, Zhang Luqing, Feng Xuechao, Zheng Yaowu
Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
Department of Immunology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou 510623, China.
Comput Struct Biotechnol J. 2020 Sep 5;18:2381-2390. doi: 10.1016/j.csbj.2020.08.030. eCollection 2020.
Disco-interacting protein 2 homolog B (Dip2B) is a member of Dip2 family encoded by gene. Dip2B has been reported to regulate murine epithelial KIT progenitor cell expansion and differentiation epigenetically via exosomal miRNA targeting during salivary gland organogenesis. However, its molecular functions, cellular activities and biological process remain unstudied. Here, we investigated the transcriptome of Dip2B-deficient mouse embryonic lung fibroblasts (MELFs) isolated from E14.5 embryos by RNA-Seq. Expression profiling identified 1369 and 1104 differentially expressed genes (DEGs) from and MELFs in comparisons to wild-type ( ). Functional clustering of DEGs revealed that many gene ontology terms belong to membrane activities such as 'integral component of plasma membrane', and 'ion channel activity', suggesting possible roles of Dip2B in membrane integrity and membrane function. KEGG pathway analysis revealed that multiple metabolic pathways are affected in and when compared to MELFs. These include 'protein digestion and absorption', 'pancreatic secretion' and 'steroid hormone synthesis pathway'. These results suggest that Dip2B may play important roles in metabolism. Molecular function analysis shows transcription factors including genes, bHLH-genes, and Forkhead-genes are significantly down-regulated in MELFs. These genes are critical in embryo development and cell differentiation. In addition, Dip2B-deficient MELFs demonstrated a reduction in cell proliferation and migration, and an increase in apoptosis. All results indicate that Dip2B plays multiple roles in cell proliferation, migration and apoptosis during embryogenesis and may participate in control of metabolism. This study provides valuable information for further understanding of the function and regulatory mechanisms of Dip2B.
Disco相互作用蛋白2同源物B（Dip2B）是由该基因编码的Dip2家族成员。据报道，Dip2B在唾液腺器官发生过程中通过外泌体miRNA靶向作用，在表观遗传上调节小鼠上皮KIT祖细胞的扩增和分化。然而，其分子功能、细胞活性和生物学过程仍未得到研究。在这里，我们通过RNA测序研究了从E14.5胚胎中分离出的Dip2B缺陷型小鼠胚胎肺成纤维细胞（MELF）的转录组。表达谱分析确定，与野生型相比，来自Dip2B缺陷型和Dip2B敲除型MELF的差异表达基因（DEG）分别有1369个和1104个。DEG的功能聚类显示，许多基因本体术语属于膜活动，如“质膜的整合成分”和“离子通道活性”，这表明Dip2B在膜完整性和膜功能中可能发挥作用。KEGG通路分析显示，与野生型MELF相比，Dip2B缺陷型和Dip2B敲除型中的多个代谢通路受到影响。这些通路包括“蛋白质消化和吸收”、“胰腺分泌”和“类固醇激素合成途径”。这些结果表明，Dip2B可能在代谢中发挥重要作用。分子功能分析表明，包括某些基因、bHLH基因和叉头基因在内的转录因子在Dip2B缺陷型MELF中显著下调。这些基因在胚胎发育和细胞分化中至关重要。此外，Dip2B缺陷型MELF表现出细胞增殖和迁移减少，凋亡增加。所有结果表明，Dip2B在胚胎发生过程中的细胞增殖、迁移和凋亡中发挥多种作用，可能参与代谢的调控。本研究为进一步了解Dip2B的功能和调控机制提供了有价值的信息。
