ARID5B promoted the histone demethylation of SORBS2 and hampered the metastasis of ovarian cancer

Ovarian cancer (OVCA) is the 4th most common female tumor after breast cancer, cervical cancer, and endometrial cancer, and now is mainly treated with debulking surgery and postoperative cisplatin and paclitaxel-based combination chemotherapy regimens. However, OVCA is insidious in its development and recurrence occurred in some patients after treatment. It is of great significance to study the pathogenesis of ovarian cancer and identify more biomarkers. Recently, the role of histone methyltransferase (HMT) and histone demethylase (HDM) in oncogenesis and development of malignant tumors has raised attention. Unlike other JMJC demethylases that have both JMJC and ARID domains in a single molecule, PHF2 requires assembly into a complex with a DNA-binding subunit (ARID5B) and exerts its enzymatic activity. Therefore, the aim of this manuscript is to investigate the role of histone demethylases ARID5B-PHF2 complex in the metastasis of OVCA. As result, we found ARID5B and PHF2 are both low expressed in OVCA tumor tissues and cell lines and associated with diagnosis and prognosis. Also, ARID5B suppressed rearrangement of the cytoskeleton in the process of EMT in OVCA cell lines. The role of PHF2 as a tumor suppressor was also confirmed both in vivo and in vitro. SORBS2 is low expressed in OVCA tumor tissues and cell lines and associated with diagnosis and prognosis. The expression of SORBS2 is positively corelated with the expression of ARID5B and PHF2. The promoter of SORBS2 is proved combined with ARID5B. The expression of SORBS2 was increased due to ARID5B-PHF2 complex promoted the histone demethylation by mainly binding in site H3K36me2 and therefore promoting the transcription of SORBS2. In conclusion, ARID5B-PHF2 complex promoted the histone demethylation of SORBS2 by mainly bind in site H3K36me2 and therefore promote the transcription of SORBS2 then hampered the process of EMT and tumor generation of OVCA. These results provided a new perspective on the molecular mechanisms of OVCA development and offered a new target of clinical diagnose and treatment of OVCA.