Upregulation of KDM2A induced by HPV16 E7 promotes cervical cancer cell proliferation and invasion and is correlated with poor prognosis in patients with cervical cancer.
Finally, the analysis of JHDM1A acetylation on osteosarcoma cell proliferation and invasion, along with tumor growth pointed out that acetylation of JHDMIA inhibited the proliferation and invasion of osteosarcoma HOS cells, as well as suppressed the tumor growth of osteosarcoma.
Upregulation of TET2 in the KDM2A-depleted cells induces the re-activation of two TET downstream tumor suppressor genes, epithelial cell adhesion molecule (EpCAM) and E-cadherin, and inhibits migration and invasion.
Silencing KDM2A with small interfering RNAs demonstrated increased invasion and migration of breast cancer cells by suppressing a subset of matrix metalloproteinases (MMP-2, -9, -14 and -15), as seen by real-time PCR.
Similar to their previously reported functions in other cell types, CDK6 and NANOS1 were required for the proliferation and invasion, respectively, of KDM2A-overexpressing NSCLC cells.
Therefore, KDM2A functions as a tumor activator in cervical cancer pathogenesis by binding miR-132 promoter and abrogating its tumor suppressive function.
Finally, the analysis of JHDM1A acetylation on osteosarcoma cell proliferation and invasion, along with tumor growth pointed out that acetylation of JHDMIA inhibited the proliferation and invasion of osteosarcoma HOS cells, as well as suppressed the tumor growth of osteosarcoma.
Our data revealed that KDM2A functions as a tumor oncogene, and the downregulation of KDM2A expression regulates EMT and EOC progression, providing a valuable prognostic marker and potential target for the treatment of EOC patients.
Taken together, we demonstrate for the first time that TET2 is a direct repression target of KDM2A and reveal a novel mechanism by which KDM2A promotes DNA methylation and breast cancer progression via the inhibition of a DNA demethylase.