Control by a hair's breadth: the role of microRNAs in the skin

Abstract

MicroRNAs have continued to attract enormous interest in the scientific community ever since their discovery. Their allure stems from their unique role in posttranscriptional gene expression control as well as their potential application as therapeutic targets in various disease pathologies. While much is known concerning their general biological function, such as their interaction with RNA-induced silencing complexes, many important questions still remain unanswered, especially regarding their functions in the skin. In this review, we summarize our current knowledge of the role of microRNAs in the skin in order to shine new light on our understanding of cutaneous biology and emphasize the significance of these small, single-stranded RNA molecules in the largest organ of the human body. Key events in epidermal and hair follicle biology, including differentiation, proliferation, and pigmentation, all involve microRNAs. We explore the role of microRNAs in several cutaneous processes, such as appendage formation, wound-healing, epithelial-mesenchymal transition, carcinogenesis, immune response, and aging. In addition, we discuss current trends in research and offer suggestions for future studies.

Fig. 1

History of microRNA research. Timeline of breakthrough discoveries in the young field of microRNA biology with a dermatology focus

Fig. 2

Evolutionary expansion of microRNAs in deuterostomes. Deuterstomes and protostomes share an ancient set of microRNAs, including let-7 family members, miR-31, and miR-34. Several waves of microRNA expansion occurred during deuterstome diversification, most notably associated with the emergence of vertebrates and placentals. The vast majority of microRNAs discussed in this review are either vertebrate or placental specific. For reasons of space and simplicity, only microRNAs up to number miR-375 were included

Fig. 3

The palladium of differentiation hypothesis: gatekeepers of the differentiated phenotype. MicroRNAs function as roadblocks to proliferation set up after the decision to differentiate has been made. In the epidermis, miR-203, let-7, and miR-125b work together with other highly expressed microRNAs to prevent the system from drifting back to a basal cell fate (blue cells) by suppressing genes associated with the basal layer cell phenotype: lin-41/TRIM71, FGFR2, P63, and cell cycle-related genes

Fig. 4

MicroRNAs in epithelial-mesenchymal transition (EMT). MicroRNAs regulate EMT by suppressing transcription factors and pathways that mediate the transition from the epithelial to mesenchymal phenotype. In turn, these microRNAs are regulated by other pathways

Fig. 5

Model of miR-21 function. miR-21, the prototypic oncomiR, promotes tumorigenesis by targeting the mRNA transcripts of molecules involved in the negative control of Ras signaling: PTEN, Spry1, and Grhl3. miR-21 is also upregulated by TGF-β and downregulated by BMP4. Conversely, competitive endogenous RNAs (ceRNAs) suppress tumorigenesis by protecting PTEN mRNA from microRNAs, such as miR-21

Fig. 6

melano-miRs: miR-214, miR-211, miR-221/222, and the miR-17–92 cluster. Summary of the roles each of these four microRNAs play in melanoma

Fig. 7

Yin and Yang of aging and cancer: regulating the balance. MicroRNAs prevent systems from falling off of the edge into chaos. By contributing to the robust nature of genetic programs, microRNAs may help to maintain homeostasis. Several microRNAs associated with aging and cancer are shown