MYEOV Is a Novel Marker of Differentiated Corneal Epithelium

Myeloma overexpressed gene (MYEOV) was initially identified as a gene amplified in several malignancies and was found to promote cell proliferation and metastasis. Our previous comparative RNA sequencing and epigenetic analyses revealed high MYEOV levels in differentiated corneal epithelial cells and showed that TET2 epigenetically regulated MYEOV expression. In the current study, we aimed to further characterize the expression and regulation of MYEOV in the human ocular surface.

MYEOV expression was examined by immunostaining of the human corneas and by analysis of the publicly available single-cell RNA sequencing data. Gene knockdown (KD) of MYEOV and the regulators of corneal epithelial differentiation, PAX6 and KLF4, in in vitro-expanded corneal epithelial cells was performed using siRNA transfection. Protein expression levels were examined by western blot. MYEOV KD cells were subjected to colony-forming and EdU cell proliferation assays and RNA sequencing analysis.

Human cornea immunostaining revealed strong MYEOV expression in the KRT12-positive differentiated corneal epithelial cells, whereas the majority of KRT13-positive differentiated conjunctival epithelial cells were MYEOV negative. MYEOV expression was not detected in the other surface ectoderm-derived epithelia, such as skin and oral mucosa. Both PAX6 KD and KLF4 KD resulted in a reduction of MYEOV and KRT12 protein expression. MYEOV KD decreased cell proliferation.

Our study revealed specific high MYEOV expression in KRT12-positive corneal epithelial cells among surface ectoderm-derived epithelia. Similar to KRT12, MYEOV expression is regulated by PAX6 and KLF4. Functionally, MYEOV regulates the proliferation of transient amplifying cells in the cornea.