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- Title
The long noncoding RNA EMBP1 inhibits the tumor suppressor miR-9-5p and promotes renal cell carcinoma tumorigenesis.
- Authors
Yejing Hong; Zhongming Yuan; Rongzhong Huang; Zhiqin Wu; Yongyong Li
- Abstract
Introduction and objectives: Long non-coding RNAs (lncRNAs) have garnered interest because of their roles in cancer progression. We aimed to explore the role of the lncRNA embigin pseudogene 1 (EMBP1)-miR-9-5p axis in renal cell carcinoma (RCC). Materials and methods: Expression profiling of miR-9-5p and EMBP1 were performed in RCC cell lines and tumor samples. To evaluate miR-9-5p and EMBP1's role in proliferation, invasion, migration, and colony formation, we performed in vitro assays along with studies in a xenograft tumor model. In silico binding site analysis using the RNA22 algorithm, RNAimmunoprecipitation (RIP), and luciferase reporter assays were used to validate a direct interaction between EMBP1 and miR-9-5p. Changes in key proteins were also analyzed. Results: miR-9-5p was significantly down-regulated, and EMBP1 was significantly upregulated, in RCC cell lines and tumor tissue. The clinicopathological characteristics of RCC patients significantly correlated with their expression. Overexpression of miR-9-5p or EMBP1 suppression in RCC cell lines significantly retarded their proliferative, migratory, and invasive behavior, in addition to promoting apoptosis and cell-cycle arrest. EMBP1 directly binds to and negatively regulates miR-9-5p. The EMBP1-miR-9-5p axis dysregulated the expression of the epithelial-to-mesenchymal transition (EMT) markers E-cadherin, claudin, and vimentin, the stemness markers KLF4 and Nanog, and the cell cycle checkpoint gene cyclin E2 (CCNE2) and its downstream mediator E2F1. miR-9-5p overexpression or EMBP1 suppression inhibited xenograft tumor growth in vivo, effects that were abrogated by CCNE2 overexpression. Conclusions: Our findings suggest an important role of the EMBP1/miR-9-5p axis dysregulation in RCC tumor progression.
- Subjects
RENAL cell carcinoma; BINDING site assay; NON-coding RNA; EPITHELIAL-mesenchymal transition; CADHERINS; TUMOR growth; CANCER cell growth
- Publication
Nefrologia, 2020, Vol 40, Issue 4, p429
- ISSN
0211-6995
- Publication type
Article
- DOI
10.1016/j.nefro.2019.12.004