MiR-122 inhibits epithelial mesenchymal transition by regulating P4HA1 in ovarian cancer cells
MiR-122 inhibits epithelial mesenchymal transition by regulating P4HA1 in ovarian cancer cells
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DOI：
10.1002/cbin.11052
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发表时间：
2018-11-01
影响因子：
3.9
通讯作者：
Cheng, Jianxin
中科院分区：
文献类型：
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作者：
Duan, Yanan;Dong, Yinghui;Cheng, Jianxin
卵巢癌是妇科最常见的恶性肿瘤之一，发病率和死亡率都很高。Hsa-miR-122- 5 p（miR-122）已被报道在多种癌症中具有肿瘤抑制作用。在这项研究中，miR-122在卵巢癌细胞中过表达，表型实验证明miR-122抑制SKOV 3和OVCAR 3细胞的迁移和侵袭。MiR-122还抑制上皮间质转化（EMT），通过E-钙粘蛋白、波形蛋白、基质金属蛋白酶（MMP）2和MMP 14的表达变化来证明。脯氨酰-4-羟化酶亚基α-1（P4 HA 1）被鉴定为miR-122的靶点，并被miR-122下调。miR-122诱导的迁移、侵袭和EMT的升高被P4 HA 1恢复。miR-122抑制SKOV 3细胞在裸鼠腹腔内的转移。综上所述，我们首次发现miR-122通过靶向P4 HA 1抑制卵巢癌细胞的迁移、侵袭、EMT和腹腔转移，为发现miR-122和P4 HA 1作为卵巢癌潜在的诊断标志物和治疗靶点提供了线索。
Ovarian cancer is one of the most common gyneacologic malignancies, with high morbidity and high mortality. Hsa-miR-122-5p (miR-122) has been reported with tumor-suppressing roles in various cancers. In this study, miR-122 was overexpressed in ovarian cancer cells, and phenotypic experiments demonstrated that miR-122 inhibited migration and invasion in SKOV3 and OVCAR3 cells. MiR-122 also suppressed epithelial mesenchymal transition (EMT), evidenced by expression changes of E-cadherin, vimentin, matrix metalloproteinase (MMP)2, and MMP14. Prolyl-4-hydroxylase subunit alpha-1 (P4HA1) was identified as a target of miR-122, and downregulated by miR-122. MiR-122-induced the elevation of migration, invasion, and EMT were recovered by P4HA1. Additionally, miR-122 restrained the tumor metastasis of SKOV3 cells in peritoneal cavity of nude mice. In summary, we demonstrated that miR-122 inhibited migration, invasion, EMT, and metastasis in peritoneal cavity of ovarian cancer cells by targeting P4HA1 for the first time, which shed lights on the discovery of miR-122 and P4HA1 as possible potential diagnostic markers and therapeutic targets for ovarian cancer.