Thorac Cancer. 2020 Aug 6. doi: 10.1111/1759-7714.13605. Online ahead of print.
BACKGROUND: Long non-coding RNA-urothelial carcinoma associated 1 (LncRNA-UCA1) is a crucial oncogene that is deregulated in many types of cancers. However, the mechanism of UCA1 function, especially for its posttranscriptional regulation in lung cancer, remains unclear.
METHODS: miRCode was used to predict potential miRNA candidates that might target UCA1. The targets of miR-138 and miR-193 on UCA1 and CDK6 were verified by luciferase reporter analysis. Western blotting was used to detect protein levels. The RNA level was evaluated using quantitative real-time polymerase chain reaction (PCR). Proliferation, wound healing, and transwell invasion assays were performed to assess cell proliferation and invasion abilities. Correlations between miR-138 or miR-193 and UCA1 in lung cancer tissues was assessed using quantitative real-time PCR.
RESULTS: miR-138 and miR-193 specifically targeted and regulated lncRNA-UCA1. MiR-138 and miR-193 both suppressed cell proliferation and cell cycle progression. Moreover, miR-138 and miR-193 inhibited cell migration and invasion. Overexpression of UCA1 reversed the proliferation, migration, and invasion suppression effects of miR-138 or miR-193. Furthermore, miR-138/193 affected the expression of UCA1 downstream genes. UCA1 regulated the expression of CDK6 as a miR-138 and miR-193 common target. In human lung cancer tissues, our study showed a significant negative correlation between miR-138 or miR-193 and UCA1 in lung cancer tissues.
CONCLUSIONS: Our results demonstrated that miR-138 and miR-193 affect cell function by directly targeting and regulating UCA1 in lung cancer.