The field of dermatology is riddled with many problems that expect solutions from modern biomedicine. Several biologicals/biotherapeutical approaches such as anti-TNFalpha antibodies have already made their impact in the daily treatment of dermatology patients. However, many challenges are still ahead. We still have to fill many gaps in our understanding of biological processes in the skin. For example until recently, an entire class of small regulatory RNA molecules, microRNAs, had remained undetected. Their emergence as important players in virtually all tissues and signaling pathways has led us to explore their significance for skin biology. In our proposal we will focus on one microRNA, miR-31, with an exceptional expression pattern in many skin diseases. This finding prompted us to address the functional significance of miR-31 in epidermal homeostasis, aberrant growth control, wound healing, stress response and hair growth. Its involvement in the regulation of major skin signaling pathways such as TNFa, TGFb and BMP signaling makes it a central node for the control of epithelial-mesenchymal transitions. We have identified a crucial role of miR-31 in hair folliculogenesis, hair growth, nail growth, and the response to wounding and the phorbol ester, TPA. TNFa, EGF and FGF7 can induce miR-31 expression and TGFb stimulates the expression of miR-31 precursors. Based on our existing mouse model of miR-31 overexpression and our preliminary data, we have developed a research plan aimed to establish miR-31 as an important regulator of such processes as EMT, proliferation and motility in keratinocytes. Thereby, we will be able to judge the potential of miR-31 as a therapeutic target for skin diseases with defects in these processes. We plan to use our existing mouse model and establish novel tools in this proposal to apply to our career-long goal to translate this knowledge into therapeutic potential of miR-31 using miR-31 inhibitors in vivo.
In Specific Aim 1 of this current research plan, we will test our hypothesis that miR-31 is a key regulator of hair growth and the response of the skin to challenges such as wounding.
In Specific Aim 2, we will address the important issue of identifying miR-31 target genes to understand miR-31 mediated processes. And in Specific Aim 3, we will test our hypothesis that miR-31 regulates epithelial-mesenchymal interactions and transitions, EMI and EMT. Furthermore, we will test whether miR-31 buffers certain expression patterns and signaling pathways against unwanted fluctuations and define which pathways exactly are influenced by miR-31 in addition to EMT and hair growth regulating signaling networks.

Public Health Relevance

The development of new therapeutic approaches has been invigorated by the discovery of small RNA molecules that can regulate gene expression and many important biological processes including all the major dermatological diseases. These small RNA molecules, called microRNAs, are formidable therapeutic targets and tools due to their size and mechanism of action. We have identified the microRNA miR-31 as potential prime candidate for therapeutic interventions due to its expression pattern, impact on events in the skin such as hair growth, its association with skin carcinogenesis, skin aging, and aberrant growth in many inflammatory disorders.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Baker, Carl
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Tian, Yuhua; Ma, Xianghui; Lv, Cong et al. (2017) Stress responsive miR-31 is a major modulator of mouse intestinal stem cells during regeneration and tumorigenesis. Elife 6:
Luan, Liming; Shi, Jianyun; Yu, Zhengquan et al. (2017) The major miR-31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation. Exp Dermatol 26:497-504
Edmonds, Mick D; Boyd, Kelli L; Moyo, Tamara et al. (2016) MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer. J Clin Invest 126:349-64
Koumangoye, Rainelli B; Andl, Thomas; Taubenslag, Kenneth J et al. (2015) SOX4 interacts with EZH2 and HDAC3 to suppress microRNA-31 in invasive esophageal cancer cells. Mol Cancer 14:24
Ning, Matthew S; Andl, Thomas (2015) Concise review: custodians of the transcriptome: how microRNAs guard stemness in squamous epithelia. Stem Cells 33:1047-54
Ning, Matthew S; Kim, Annette S; Prasad, Nripesh et al. (2014) Characterization of the Merkel Cell Carcinoma miRNome. J Skin Cancer 2014:289548
Ning, Matthew S; Andl, Thomas (2013) Control by a hair's breadth: the role of microRNAs in the skin. Cell Mol Life Sci 70:1149-69