EGF-Mediated Overexpression of Myc Attenuates miR-26b by Recruiting HDAC3 to Induce Epithelial-Mesenchymal Transition of Lens Epithelial Cells.

The previous study has demonstrated that epidermal growth factor (EGF) and EGF receptor (EGFR) signaling plays a critical role in the development of posterior capsule opacification (PCO) through regulating lens epithelial cells (LECs) proliferation. Recent studies have suggested that the residual LECs undergo proliferation and migration, and epithelial-mesenchymal transition (EMT) is the important cause of PCO formation after cataract surgery. EMT of LECs is considered to be playing a central role in the pathogenesis of PCO. In the present study, we investigated whether and how EGF may regulate EMT of LECs. First, we demonstrated that EGF and EGFR signaling induces Myc overexpression in primary human lens epithelial cells (HLECs). In turn, Myc overexpression could inhibit miR-26b by recruitment of HDAC3. Consequently, the downregulated expression of miR-26b increased the expression of EZH2 in primary HLECs. Mechanistically, miR-26b directly controls EZH2 expression by targeting its 3'-UTR in HLECs by luciferase reporter assays. Finally, we demonstrated that EGF induces the expression of EMT markers in primary HLECs via a miR-26b-dependent mechanism. In summary, EGF activated Myc and Myc overexpression inhibited miR-26b by recruitment of HDAC3, which in turn induced the expression of EZH2 and promoted the progression of EMT in HLECs.