Department of Traditional Chinese Medicine, The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Radiotherapy and Chemotherapy, The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Neoplasma. 2018 Nov 15;65(6):881-887. doi: 10.4149/neo_2018_171206N803. Epub 2018 Jun 17.
Nuclear receptor interacting protein (NRIP1), also known as RIP140, is a transcriptional co-regulator required for the maintenance of energy homeostasis and ovulation. Although several studies have identified roles for NRIP1 in various cell processes, the biological functions of NRIP1 in esophageal squamous cell carcinoma (ESCC) remain unknown. Herein, we demonstrate that NRIP1 inhibits the migration and invasion of ESCC cells. Further mechanistic studies revealed that NRIP1 is directly targeted by miR-548-3p and miR-576-5p. We then identified that miR-548-3p and miR-576-5p regulate the migration and invasion of ESCC cells by inhibiting NRIP1 expression. Interestingly, the expression of miR-548-3p and miR-576-5p in ESCC cell lines and ESCC tissues is up-regulated and NRIP1 is down-regulated relative to controls. A statistically significant inverse association was found between the expression levels of miR-548-3p/miR-576-5p and NRIP1. These combined results reveal novel functions for miR-548-3p, miR-576-5p, and NRIP1 in regulating ESCC cell migration and invasion which are important functions for the metastatic process in esophageal cancer.
核受体相互作用蛋白(NRIP1),也称为 RIP140,是维持能量平衡和排卵所必需的转录共调节剂。尽管有几项研究已经确定了 NRIP1 在各种细胞过程中的作用,但 NRIP1 在食管鳞状细胞癌(ESCC)中的生物学功能仍然未知。在此,我们证明 NRIP1 抑制 ESCC 细胞的迁移和侵袭。进一步的机制研究表明,NRIP1 是由 miR-548-3p 和 miR-576-5p 直接靶向的。然后,我们确定 miR-548-3p 和 miR-576-5p 通过抑制 NRIP1 表达来调节 ESCC 细胞的迁移和侵袭。有趣的是,miR-548-3p 和 miR-576-5p 在 ESCC 细胞系和 ESCC 组织中的表达上调,而 NRIP1 的表达下调。miR-548-3p/miR-576-5p 和 NRIP1 的表达水平之间存在统计学上显著的负相关关系。这些综合结果揭示了 miR-548-3p、miR-576-5p 和 NRIP1 在调节 ESCC 细胞迁移和侵袭中的新功能,这些功能对于食管癌的转移过程很重要。