Long non-coding RNA UCA1 promotes malignant phenotypes of renal cancer cells by modulating the miR-182-5p/DLL4 axis as a ceRNA

• Published in: Molecular cancer 2020-01, Vol.19 (1), p.18-17, Article 18
• Main Authors: Wang, Wei, Hu, Wentao, Wang, Ya, An, Yong, Song, Lei, Shang, Panfeng, Yue, Zhongjin
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Analysis; Angiogenesis; Animals; Apoptosis; Biological markers; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Bladder cancer; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cancer; Cancer cells; Cell adhesion & migration; Cell growth; Cell migration; Cell Proliferation; ceRNA; Colorectal cancer; Development and progression; DLL4; Experiments; Female; Flow cytometry; Gene Expression Regulation, Neoplastic; Genetic aspects; Humans; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Kidneys; Ligands; Luciferase; Male; Membranes; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miR-182-5p; miRNA; Molecular modelling; Non-coding RNA; Novels; Phenotypes; Plasmids; Prognosis; Proteins; Renal cancer; Renal cell carcinoma; RNA; RNA, Long Noncoding - genetics; Survival Rate; Therapeutic applications; Transcription; Tumor cell lines; Tumor Cells, Cultured; Tumorigenesis; Tumorigenicity; Tumors; UCA1; Urothelial cancer; Xenograft Model Antitumor Assays
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-020-1132-x

Accumulating literatures have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Urothelial cancer associated 1 (UCA1) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the molecular mechanism of UCA1 in renal cancer is still needed to further explore. The relative expression level of UCA1 was determined by Real-Time qPCR in a total of 88 patients with urothelial renal cancer and in different renal cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of UCA1 and miR-182-5p on renal cancer cell proliferation, migration, apoptosis and tumorigenicity. Comprehensive transcriptional analysis, dual-luciferase reporter assay and western blot etc. were performed to explore the molecular mechanisms underlying the functions of UCA1. In this study, we found that UCA1 was significantly up-regulated in renal cancer. Moreover, increased UCA1 expression was positively correlated with differentiation and advanced TNM stage. Further experiments demonstrated that knockdown of UCA1 inhibited malignant phenotypes and Notch signal path of renal cancer cells, and miR-182-5p was reverse function as UCA1. UCA1 functioned as a miRNA sponge to positively regulate the expression of Delta-like ligand 4(DLL4) through sponging miR-182-5p and subsequently promoted malignant phenotypes of renal cancer cells, thus UCA1 playing an oncogenic role and miR-182-5p as an antioncogenic one in renal cancer pathogenesis. UCA1-miR-182-5p-DLL4 axis is involved in proliferation and progression of renal cancer. Thus, this study demonstrated that UCA1 plays a critical regulatory role in renal cancer cell and UCA1 may serve as a potential diagnostic biomarker and therapeutic target of renal cancer.