Regulation of miRNA Processing and miRNA Mediated Gene Repression in Cancer

Abstract

The majority of human protein-coding genes are predicted to be targets of miRNA-mediated post-transcriptional regulation. The widespread influence of miRNAs is illustrated by their essential roles in all biological processes. Regulated miRNA expression is essential for maintaining cellular differentiation; therefore alterations in miRNA expression patterns are associated with several diseases, including various cancers. High-throughput sequencing technologies revealed low level expressing miRNA isoforms, termed isomiRs. IsomiRs may differ in sequence, length, target preference and expression patterns from their parental miRNA and can arise from differences in miRNA biosynthesis, RNA editing, or SNPs inherent to the miRNA gene. The association between isomiR expression and disease progression is largely unknown. Misregulated miRNA expression is thought to contribute to the formation and/or progression of cancer. However, due to the diversity of targeted transcripts, miRNAs can function as both tumor-suppressor genes and oncogenes as defined by cellular context. Despite this, miRNA profiling studies concluded that the differential expression of particular miRNAs in diseased tissue could aid the diagnosis and treatment of some cancers.

The distinct transcriptomes of slow and fast adult muscles are delineated by noncoding RNAs

“…We found that muscle RNA landscapes differed genome wide between fast and slow muscles, and those differences were predominantly delineated by DE noncoding RNAs, rather than muscle transcription factors, alternative splicing, or APA. Noncoding small RNAs and miRs target mRNA to the surveillance machinery (35). Our results revealed that more than one quarter of the genes with higher expression in quadriceps were targets for miRs high in the soleus.…”

“…Most of the DE target genes were miR23a/b targets. The expression of miR-23a/b was not limited to skeletal muscles, but in skeletal muscles, they are involved in muscle atrophy and muscle exercise, and they regulated the expression of mitochondrial genes (35,37,38). The miRs high in quadriceps, miR-1199, miR-8116, and miR-7666, have not been characterized in any detail, and their biologic roles should be explored in future studies.…”

“…The mRNA surveillance pathway (3015) was significantly affected. That pathways is regulated by exportins (Xpo), which mediate nuclear export of pre-microRNAs and affect miR expression levels (35). The Xpo4, Xpo5, and Xpo6 genes showed higher expression levels in the soleus, and their expression levels correlated with miR-1a, miR-23a, miR-206, and miR-133b levels.…”

Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts

“…Similar to protein coding genes, most miRNA genes are transcribed by RNA polymerase II to form terminal and poly-adenylated RNA precursors or primary transcripts (pri-miRNAs) [3]. Stress-signals in cancer cells regulate the production of particular pri-miRNAs by controlling the functionality of certain transcription factors [4].…”

RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs

“…Due to their extensive influence on gene regulation, miRNA function and expression are spatially and developmentally controlled, which is essential for defining and maintaining cellular differentiation and identity. Therefore, it is not surprising that miRNA expression is altered in most disease states and has been found to play major roles in the development and progression of several diseases [20][21][22][23][24] and are actively being investigated and developed for clinical applications [25].…”