肿瘤干细胞的“干性”是卵巢癌发生发展和转移复发等始作俑者。Midkine（MK）作为一种维持早期胚胎干细胞全能性和更新分化的重要因子，在包括卵巢癌等多种肿瘤中高表达，但其与肿瘤干细胞的关系及机理尚不明确。我们前期研究结果表明， MK可以促进间充质干细胞和卵巢癌细胞中“干性”关键因子（SOX2,OCT4, NICD等）的核内表达，并且MK在原代卵巢癌CD44+CD117+CD133+阳性肿瘤干细胞中的表达显著高于总癌细胞，但低于CD44-CD117-CD133-肿瘤细胞。深入研究发现，超高MK会抑制SOX2/OCT4下游启动基因的表达，这提示MK在维持肿瘤干细胞“干性”存在两面性。通过生物信息学分析，我们发现MK可以调节非编码RNA进而负反馈抑制卵巢癌干细胞的“干性”，但具体机制不明。上述强烈提示，MK可能通过其受体及非编码RNA双向调控以维持卵巢癌肿瘤干细胞的“干性”，促进卵巢癌发生发展。

The “stemness” of cancer stem cell has been known as the major reason in ovarian cancer, which takes improtant roles in cancer development, metastasis, recurrence and drugs resistance. Midkine, as a key factor for maintaining the pluripotency and prolifiation of embryonic stem cell, can also be detected in kinds of cancer beside ovarian cancer, while the funtion of MK in cancer stem cell hasn’t been understanded. Our privouse studies have been found that MK could enhance the nuclear expression of stemness genes, as SOX2, OCT4, NICD and TGF-β, in mesenchymal stem cells and ovarian cancer. Moreover, MK expression in CD44+CD117+ and CD44+CD133+ ovarian cancer cells in significantly higher than in the total cancer cells, but clear lower than CD44-CD117- and CD44-CD133-, respectively. Further studies have shown that ultrahigh MK could inhibit SOX2/OCT4 downstream genes expression, those data indicated that MK might participate in stemness maintaining through positive and negative regulation. Combined with bioinformatics analysis, we figured out that non-coding RNAs could regulate by MK, then participated into the negative regulation of stemness in cancer stem cell, but the specific mechanisms have not been cleared. According to those data, MK might maintain the stemness of cancer stem cells in ovarian cancer through MK receptors and non-coding RNAs, then promote the development of ovarian cancer.