Pathania Anup S
Department of Biochemistry and Molecular Biology & The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Cancers (Basel). 2023 May 19;15(10):2833. doi: 10.3390/cancers15102833.
According to the World Health Organization, every year, an estimated 400,000+ new cancer cases affect children under the age of 20 worldwide. Unlike adult cancers, pediatric cancers develop very early in life due to alterations in signaling pathways that regulate embryonic development, and environmental factors do not contribute much to cancer development. The highly organized complex microenvironment controlled by synchronized gene expression patterns plays an essential role in the embryonic stages of development. Dysregulated development can lead to tumor initiation and growth. The low mutational burden in pediatric tumors suggests the predominant role of epigenetic changes in driving the cancer phenotype. However, one more upstream layer of regulation driven by ncRNAs regulates gene expression and signaling pathways involved in the development. Deregulation of ncRNAs can alter the epigenetic machinery of a cell, affecting the transcription and translation profiles of gene regulatory networks required for cellular proliferation and differentiation during embryonic development. Therefore, it is essential to understand the role of ncRNAs in pediatric tumor development to accelerate translational research to discover new treatments for childhood cancers. This review focuses on the role of ncRNA in regulating the epigenetics of pediatric tumors and their tumor microenvironment, the impact of their deregulation on driving pediatric tumor progress, and their potential as effective therapeutic targets.
据世界卫生组织统计，全球每年估计有超过40万例新发癌症病例发生在20岁以下的儿童身上。与成人癌症不同，儿童癌症由于调节胚胎发育的信号通路发生改变，在生命早期就会发展，环境因素对癌症发展的影响不大。由同步基因表达模式控制的高度有序的复杂微环境在发育的胚胎阶段起着至关重要的作用。发育失调会导致肿瘤的发生和生长。儿童肿瘤中低突变负担表明表观遗传变化在驱动癌症表型方面起主要作用。然而，由非编码RNA驱动的另一个上游调控层调节参与发育的基因表达和信号通路。非编码RNA的失调会改变细胞的表观遗传机制，影响胚胎发育过程中细胞增殖和分化所需的基因调控网络的转录和翻译谱。因此，了解非编码RNA在儿童肿瘤发展中的作用对于加速转化研究以发现儿童癌症的新治疗方法至关重要。本综述重点关注非编码RNA在调节儿童肿瘤表观遗传学及其肿瘤微环境中的作用、其失调对推动儿童肿瘤进展的影响以及它们作为有效治疗靶点的潜力。
