Epigenetic regulation of mRNA mediates the phenotypic plasticity of cancer cells during metastasis and therapeutic resistance (Review).

ABSTRACT

Plasticity, the ability of cancer cells to transition between differentiation states without genomic alterations, has been recognized as a major source of intratumoral heterogeneity. It has a crucial role in cancer metastasis and treatment resistance. Thus, targeting plasticity holds tremendous promise. However, the molecular mechanisms of plasticity in cancer cells remain poorly understood. Several studies found that mRNA, which acts as a bridge linking the genetic information of DNA and protein, has an important role in translating genotypes into phenotypes. The present review provided an overview of the regulation of cancer cell plasticity occurring via changes in the transcription and editing of mRNAs. The role of the transcriptional regulation of mRNA in cancer cell plasticity was discussed, including DNA­binding transcriptional factors, DNA methylation, histone modifications and enhancers. Furthermore, the role of mRNA editing in cancer cell plasticity was debated, including mRNA splicing and mRNA modification. In addition, the role of non­coding (nc)RNAs in cancer plasticity was expounded, including microRNAs, long intergenic ncRNAs and circular RNAs. Finally, different strategies for targeting cancer cell plasticity to overcome metastasis and therapeutic resistance in cancer were discussed.