Zheng Hua-Chuan, Zhao Shuang, Song Yang, Ding Xiao-Qing
Department of Experimental Oncology and Animal Center, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Department of Pathology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
Oncotarget. 2017 Oct 19;8(61):103449-103464. doi: 10.18632/oncotarget.21968. eCollection 2017 Nov 28.
Here, we found that ING5 overexpression suppressed cell viability, glucose metabolism, migration, invasion and epithelial-mesenchymal transition, and induced cell arrest, apoptosis, senescence, autophagy and fat accumulation in ovarian cancer cells. ING5-mediated chemoresistance was positively linked to apoptotic resistance and chemoresistance-related gene expression. ING5 overexpression suppressed tumor growth of ovarian cancer by decreasing proliferation, and inducing apoptosis and autophagy. ING5 mRNA level was lower in ovarian cancer than normal ovary, and borderline than benign tumors ( < 0.05), and negatively correlated with vascular invasion, lymphatic invasion and FIGO staging of ovarian cancer ( < 0.05). ING5 protein was less expressed in primary cancer than normal ovary ( < 0.05). There was a negative correlation between mRNA expression and the overall or progression-free survival time of the cancer patients with Grade 2, Grade 3, and stage I cancer ( < 0.05). Immunohistochemically, ING5 was less expressed in serous and mucinous adenocarcinoma than miscellaneous subtypes, and positively correlated with dedifferentiation and ki-67 expression of ovarian cancer ( < 0.05). These data suggested that down-regulated ING5 expression might be involved in ovarian carcinogenesis possibly by suppressing aggressive phenotypes, including proliferation, tumor growth, migration, invasion, and anti-apoptosis.
在此，我们发现ING5过表达可抑制卵巢癌细胞的细胞活力、葡萄糖代谢、迁移、侵袭及上皮-间质转化，并诱导细胞停滞、凋亡、衰老、自噬和脂肪积累。ING5介导的化疗耐药与凋亡抵抗及化疗耐药相关基因表达呈正相关。ING5过表达通过降低增殖、诱导凋亡和自噬来抑制卵巢癌的肿瘤生长。ING5 mRNA水平在卵巢癌中低于正常卵巢，在交界性肿瘤中低于良性肿瘤（<0.05），且与卵巢癌的血管侵袭、淋巴侵袭和国际妇产科联盟（FIGO）分期呈负相关（<0.05）。ING5蛋白在原发性癌中的表达低于正常卵巢（<0.05）。在2级、3级和I期癌症患者中，mRNA表达与总体或无进展生存时间呈负相关（<0.05）。免疫组织化学结果显示，ING5在浆液性和黏液性腺癌中的表达低于其他亚型，且与卵巢癌的去分化和ki-67表达呈正相关（<0.05）。这些数据表明，ING5表达下调可能通过抑制包括增殖、肿瘤生长、迁移、侵袭和抗凋亡等侵袭性表型参与卵巢癌的发生。
