MYC Is Functionally Required in Both Normal and Neoplastic Meibomian Glands

Despite the clinical importance of the meibomian gland (MG), the mechanisms controlling its proliferation and differentiation remain unclear. Ocular adnexal sebaceous carcinoma (SebCA), an aggressive malignancy that most often arises from the MG, lacks well-defined oncogenic drivers, but high MYC expression has been demonstrated in both tumors and primary human cell lines. This study evaluated the ongoing dependence of MYC in the MG. MYC-modulated murine MGs were evaluated using histopathology, morphometry, immunohistochemistry, and quantitative PCR. Viability, differentiation, and proliferation were evaluated in vitro, clonogenic potential was assessed by quantifying anchorage-dependent colony formation, and MYC expression was determined using enzyme-linked immunosorbent assay and quantitative PCR. MYC-inhibited murine MGs exhibited significantly reduced cytoplasmic volume with diminished proliferation and increased apoptosis with altered lipid droplet formation relative to contralateral control eyelids. SebCA viability and clonogenicity were significantly impaired by MYC inhibition, and proliferation was significantly reduced in all cells following incubation with MYCMI6. MYCMI6 also showed the most prominent suppression of canonical MYC transcriptional targets of the three MYC inhibitors used. MYC concentration was significantly lower in MYCi361- and 10074-G5-treated cells relative to vehicle control, and relative MYC expression was significantly up-regulated in 10074-G5-treated SebCA01 cells. MYC stability, MYC transcriptional activity, and the MYC:MAX heterodimer may represent critical regulators of proliferation and differentiation in the MG, with dysregulation contributing to oncogenic potential.