KDM2B mediates the Wnt/β-catenin pathway through transcriptional activation of PKMYT1 via microRNA-let-7b-5p/EZH2 to affect the development of non-small cell lung cancer.

The significance of KDM2B in oncogenesis has been appreciated, but the mechanism behind is incompletely understood. In this work, we addressed its effects on the progression of non-small cell lung cancer (NSCLC). Overexpression of KDM2B was linked to dismal prognoses of NSCLC patients. Based on the expression levels of KDM2B in a panel of NSCLC cell lines, A549, showing lower level of expression, and SK-MES-1, showing higher levels of expression, were selected as model systems to evaluate the effect of KDM2B overexpression and KDM2B silencing, respectively. Knockdown of KDM2B hampered NSCLC cell proliferation, invasion, as well as migration, while enhanced apoptosis. Additionally, KDM2B repressed the expression of microRNA (miR)-let-7b-5p through demethylation modification of H3K36me2, thereby promoting the expression of zester homolog 2 (EZH2), the target gene of let-7b-5p in NSCLC. Moreover, EZH2 transcriptionally induced the expression of PKMYT1 to activate the Wnt/β-catenin pathway. Sh-EZH2 and sh-PKMYT1 neutralized the supporting effects of KDM2B on cell proliferation, invasion and migration. Additionally, deletion of KDM2B reduced the xenograft volumes in nude mice. In conclusion, KDM2B induces the EZH2/PKMYT1/Wnt/β-catenin axis by inhibiting the let-7b-5p expression, which promotes NSCLC growth. More investigations are essential to determine the oncogenic role of KDM2B in NSCLC.