A new insight on reciprocal relationship between microRNA expression and epigenetic modifications in human lung cancer

Abstract

Lung cancer stands among the leading causes of cancer-related death in the world. Although the molecular network implicated in lung cancer development is extensively revealed, the mortality rate is only slightly improved. MicroRNAs are small, endogenous single-stranded evolutionary conserved non-coding RNAs which involve in a wide variety of biological processes including cell growth, proliferation, metabolism, and differentiation. MicroRNAs, as novel biomarkers, have multiple functions in normal lung tissue development, and aberrant expression profiles of certain microRNAs could induce lung tumorigenesis. Similar to that of protein-coding genes, microRNA expression and function are regulated by multiple factors as well as the epigenetic network including DNA methylation and histone modification mechanisms. Furthermore, microRNAs can themselves regulate key enzymes which drive epigenetic modifications and have a pivotal effect on the cell biology. In this review, we will look into the regulatory loop linkage between microRNA expression and epigenetic modifications, and then, we will discuss the effects of epigenetics on the miRNome, as well as the role of epi-microRNAs in controlling the epigenome in human lung cancer. Better knowledge of reciprocal connection between microRNAs and epigenome will help to develop novel microRNA-orientated diagnostic, prognostic and therapeutic strategies related to human lung cancer in future.

Role of miRNAs in Melanoma Metastasis

“…miRNAs are crucial messengers of intercellular communication. The extracellular transfer of miRNAs is mediated by either protein transporters such as AGO (argonaute), HDL (high density lipoprotein), or extracellular vesicles (EV), e.g., oncosomes, ectosomes, exosomes, and melanosomes [33,47,48,49,50,51,52]. miRNA aggregation with proteins or encapsulation into EVs protect them from degradation by RNases [34,53,54,55].…”

miR‐203 inhibits cell proliferation, invasion, and migration of non‐small‐cell lung cancer by downregulating RGS17

“…MicroRNAs (miRNAs) are small non‐coding RNAs that regulate a variety of biological processes by modulating gene expression at the post‐transcriptional level . Increasing evidence suggests that miRNAs play an important role in the control of cancer cell invasion and metastasis . For example, miR‐19 triggers the epithelial–mesenchymal transition of lung cancer cells, which is accompanied by growth inhibition .…”

“…(10) Increasing evidence suggests that miRNAs play an important role in the control of cancer cell invasion and metastasis. (11)(12)(13) For example, miR-19 triggers the epithelial-mesenchymal transition of lung cancer cells, which is accompanied by growth inhibition. (14) miR-92a promotes the epithelial-mesenchymal transition through activation of the PTEN/PI3K/AKT signaling pathway in non-small-cell lung cancer (NSCLC) metastasis.…”

Regulatory Mechanisms of Epigenetic miRNA Relationships in Human Cancer and Potential as Therapeutic Targets

“…As discussed earlier, several studies using a range of cell lines have indicated overexpression of numerous miRNAs following treatment with epigenetic drugs [ 111 , 112 , 113 ]. The let-7a-3 locus is hypermethylated in normal human lung tissue, but in some lung adenocarcinomas, it becomes hypomethylated and overexpressed [ 114 ]. miRNA-mediated deregulation of DNMTs has been observed in several cancers.…”