The high mobility group AT-hook 2 (HMGA2) gene encodes a transcription factor that is expressed during embryonic development but down-regulated in adult tissues. Its re-expression in adult tissues is often associated with tumorigenesis. In this study, we found that HMGA2 is highly expressed in human cutaneous squamous cell carcinoma (SCC) cell lines and primary SCC tumors, but not in adjacent normal skin. In non-ultraviolet (UV)-irradiated mouse skin, baseline Hmga2 expression was detected in the epidermis but not in hair follicles. Following chronic UV exposure, we found activation of Hmga2 in hair follicles. UV-induced mouse skin SCC tumors displayed a ubiquitous increase in Hmga2 expression compared to non-tumor-bearing adjacent skin. In human SCC cells, decreased HMGA2 expression was linked with reduced cell proliferation following depletion of FOXM1 and TRIP13, two UV master regulator genes. Taken together, these findings highlight an important biomarker function of HMGA2 expression in UV-induced skin tumorigenesis and cell proliferation.
Bibliographical noteFunding Information:
We greatly appreciate the excellent technical assistance from Rong Du, Kevin Sun and Tao Su with cell culture, tissue procurement and RNA preparation. We are also grateful to the support from the Molecular Pathology Shared Resource at Columbia University Medical Center. This work was supported by NIH/NIAMS grant K01AR064315, the Prevent Cancer Foundation and the Hormel Foundation.
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
- UV radiation
- skin cancer