MicroRNA-145 targets in cancer and the cardiovascular system: evidence for common signaling pathways

Abstract

miRNAs are small regulatory RNAs which govern gene expression post-transcriptionally by primarily binding to the 3'-UTR of mRNA target genes. miR-145 is a well-studied miRNA that has been implicated in controlling a range of biological processes. miR-145 is expressed in a variety of tissues and cell types and acts as a tumor-suppressor by regulating target gene signaling pathways involved in different aspects of tumor growth and progression. There is also strong evidence that highlights the important functions of miR-145 in the cardiovascular system. Here, we review the mechanisms of miR-145 in tumorigenesis and cancer progression and compare and contrast with the roles of miR-145 in cardiovascular development and disease. We discuss the important targets of miR-145 in cancer and their possible link to the cardiovascular system.

Keywords: cancer; cardiovascular; miR-145; smooth muscle.

Figure 1

Tumor progression is a multi-step process and miR-145 regulates various targets at different stages of tumorigenesis. miR-145 inhibits tumors growth and angiogenesis and increases apoptosis by directly suppressing various genes. miR-145 inhibits cell invasion and tumor metastasis in various cancers.

Figure 2

Roles of miR-145 in different cardiovascular cell types. (A) In the cardiovascular system, miR-145 plays various roles in smooth muscle cells (SMCs), endothelial cells, fibroblasts, and cardiomyocytes. (B and C) The role of miR-145 in SMCs and endothelial cells is highlighted in detail. In SMCs, miR-145 expression is regulated by TGFβ-1 signaling and SRF/Myocd complex. It represses KLF4 and promotes the differentiation of SMCs. In endothelial cells, miR-145 is induced by KLF2 in response to sheer stress. Subsequently, miR-145 is exported in exosome-like vesicles to SMCs to regulate SMC phenotypes. SRF, serum response factor; KLF4, Kruppel-like factor 4; SBE, SMADs binding element.