Background: Lysine demethylase 3A (KDM3A ) has been increasingly recognized as an important epigenetic regulator involved in cancer development. This study aims to explore the relevance of KDM3A  to cervical cancer (CC) progression and the molecules involved.
Materials and Methods: Tumor and the adjacent tissues from CC patients were collected. KDM3A  expression in tissues and CC cell lines and its correlation with the survival and prognosis of patients were determined. Malignant potentials of CC cells and the angiogenesis ability of HUVECs were measured to evaluate the function of KDM3A  on CC progression. The interactions among KDM3A , H3K9me2 and ETS1 , and the binding between ETS1  and KIF14  were validated through ChIP and luciferase assays. Altered expression of ETS1  and KIF14  was introduced to explore their roles in CC development.
Results: KDM3A  was abundantly expressed in CC tissues and cells and linked to dismal prognosis of CC patients. Knockdown of KDM3A  suppressed malignant behaviors of CC cells. KDM3A  was found to increase ETS1  expression through the demethylation of H3K9me2. Overexpression of ETS1  blocked the inhibiting roles of sh-KDM3A. ETS1  could bind to the promoter region of KIF14  to trigger its transcription. Overexpression ofKIF14  aggravated the malignant behaviors of CC cells and the angiogenesis ability of HUVECs, and it activated the Hedgehog signaling pathway. Artificial activation of Hedgehog by Sag1.5 diminished the effects of sh-KDM3A. These changes were reproduced in vivo.
Conclusion: This study evidenced that KDM3A  promotes ETS1 -mediated KIF14  transcription to promote CC progression with the involvement of the Hedgehog activation.
Keywords: lysine demethylase 3A, ETS proto-oncogene 1, kinesin family member 14, Hedgehog signaling pathway, cervical cancer