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miR-122 通过调控卵巢癌细胞中的 P4HA1 抑制上皮间质转化。

MiR-122 inhibits epithelial mesenchymal transition by regulating P4HA1 in ovarian cancer cells.

机构信息

Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People's Republic of China.

Department of Oncology, Shijiazhuang First Hospital, Shijiazhuang, 050011, People's Republic of China.

出版信息

Cell Biol Int. 2018 Nov;42(11):1564-1574. doi: 10.1002/cbin.11052. Epub 2018 Sep 16.

Abstract

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.

摘要

卵巢癌是最常见的妇科恶性肿瘤之一,具有高发病率和高死亡率。hsa-miR-122-5p(miR-122)已被报道在各种癌症中具有肿瘤抑制作用。在本研究中,miR-122 在卵巢癌细胞中过表达,表型实验表明 miR-122 抑制 SKOV3 和 OVCAR3 细胞的迁移和侵袭。miR-122 还抑制上皮间质转化(EMT),表现在 E-钙黏蛋白、波形蛋白、基质金属蛋白酶(MMP)2 和 MMP14 的表达变化。脯氨酰-4-羟化酶亚基α-1(P4HA1)被鉴定为 miR-122 的靶标,并被 miR-122 下调。miR-122 诱导的迁移、侵袭和 EMT 升高被 P4HA1 恢复。此外,miR-122 抑制了 SKOV3 细胞在裸鼠腹腔中的转移。总之,我们首次证明 miR-122 通过靶向 P4HA1 抑制卵巢癌细胞在腹腔中的迁移、侵袭、EMT 和转移,这为 miR-122 和 P4HA1 作为卵巢癌潜在的诊断标志物和治疗靶点的发现提供了依据。

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