Since Cyclin D1 is known to promote cell proliferation [33], repression of Cyclin D1 would have disrupted expansion of the prospective NR layer after BHLHE40 overexpression and also via downregulation of VSX2. In cancer cell lines, BHLHE40 (DEC1) interacts with Cyclin E and stabilizes it, leading to prolonging the S phase and suppressing cell proliferation [34]. This evidence concerns the gene CCNE1 and cancer.