Crosstalk between Noncoding RNAs and the Epigenetics Machinery in Pediatric Tumors and Their Microenvironment

Abstract

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.

The ErbB Signaling Network and Its Potential Role in Endometrial Cancer

“…Non-coding RNAs (ncRNAs) are functional RNA molecules that occupy a large fraction of the genome, but they are not translated into proteins [ 108 , 112 , 113 , 114 ]. They have key roles in the regulation of gene expression at transcriptional and translational levels [ 113 , 114 ].…”

“…Non-coding RNAs (ncRNAs) are functional RNA molecules that occupy a large fraction of the genome, but they are not translated into proteins [ 108 , 112 , 113 , 114 ]. They have key roles in the regulation of gene expression at transcriptional and translational levels [ 113 , 114 ]. Moreover, they can be divided into the following categories: microRNAs (miRNAs), long noncoding RNAs (lncRNAs), small interfering RNAs (siRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), circular RNAs (circRNAs) and PIWI-interacting RNAs (piRNAs) [ 108 , 112 , 113 , 114 ].…”

“…They have key roles in the regulation of gene expression at transcriptional and translational levels [ 113 , 114 ]. Moreover, they can be divided into the following categories: microRNAs (miRNAs), long noncoding RNAs (lncRNAs), small interfering RNAs (siRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), circular RNAs (circRNAs) and PIWI-interacting RNAs (piRNAs) [ 108 , 112 , 113 , 114 ]. Among these, miRNAs and lncRNAs have crucial roles in cancer epigenetics [ 113 , 114 ].…”

“…More specifically, miRNAs are small ncRNAs, approximately 19 to 22 nucleotides in length, that regulate gene expression by posttranscriptional silencing [ 115 , 116 ]. They usually bind to the 3′-untranslated region (3′-UTR) of target messenger RNA (mRNA) molecules, resulting in either translational inhibition or mRNA degradation [ 113 , 114 , 115 , 117 ].…”

“…In contrast, lncRNAs are larger ncRNAs, more than 200 nucleotides in length, that regulate gene expression at transcriptional, post-transcriptional and epigenetic levels [ 113 , 118 , 119 ]. In particular, guide lncRNAs act by recruiting or rejecting epigenetic regulators (chromatin modifying complexes and chromatin remodeling complexes) onto specific chromosomal loci [ 120 ].…”