The function of BED finger domain of Zbed3 in regulating lung cancer cell proliferation

Abstract

Zbed3, a BED finger domain‐containing protein was found to promote cancer proliferation by regulating β‐catenin expression through interacting with Axin. But whether and how BED finger domain function in regulating cancer proliferation is unknown. We constructed five mutants of Zbed3, which lacks the Axin‐Zbed3 binding site, and the 43 to 52, 69 to 77, 87 to 92, and 97 to 104 sequences in BED finger domain, respectively and named them as Z‐A, Z1, Z2, Z3, and Z4. Transfection of both wild‐type of Zbed3 and the mutants Z1, Z3, and Z4 (P\u2009<\u20090.05), but not Z2 (P\u2009>\u20090.05) significantly upregulated β‐catenin expression in NCI‐H1299 cells. Overexpression of both wild‐type of Zbed3 and the mutants Z1, Z3, and Z4 (P\u2009<\u20090.05) but not Z2 (P\u2009>\u20090.05) significantly promoted cancer cell proliferation and invasion. The ability of proliferation (P\u2009<\u20090.05) but not invasion (P\u2009<\u20090.05) of cancer cells transfected with Z1 and Z4 was significantly lower than that with wild‐type Zbed3 and Z3. Overexpression of wild‐type Zbed3 (P\u2009<\u20090.05) but not the mutant Z‐A, which lacks the binding site with Axin and Z2 (P\u2009>\u20090.05) significantly upregulated the interaction of Axin and Zbed3, β‐catenin expression and the activity of Wnt signaling. Both overexpression of wild‐type Zbed3 and the mutant Z1 and Z4 significantly upregulated the activity of Wnt signaling and promoted cancer cell proliferation (P\u2009<\u20090.05) but only overexpression of wild‐type Zbed3 (P\u2009<\u20090.05), but not the mutant Z1, and Z4 (P\u2009>\u20090.05), significantly upregulated the expression of proliferating cell nuclear antigen (PCNA) in NCI‐H1299 cells. These results indicate that Zbed3 may promote lung cancer cell proliferation through regulating PCNA expression besides regulating β‐catenin expression and BED finger domain can impact on this function.