LncRNA UNC5B-AS1 promotes malignant progression of prostate cancer by competitive binding to caspase-9

Abstract

Objective: This study aims to investigate the expression of LncRNA UNC5B-AS1 in prostate cancer (PCa) and to further investigate whether it can prompt malignant progression of PCa via regulating caspase-9.

Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to examine UNC5B-AS1 expression in 50 pairs of tumor tissue specimens and paracancerous ones collected from PCa patients, and the interplay between UNC5B-AS1 expression and clinical indicators of PCa was also analyzed. Meanwhile, UNC5B-AS1 levels in PCa cell lines were also further verified by qRT-PCR. In addition, UNC5B-AS1 knockdown model was constructed using lentivirus in PCa cell lines, and cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), transwell and flow cytometry assays were performed to figure out the impact of UNC5B-AS1 on the biological function of PCa cells. Finally, cell recovery experiment was conducted to explore the underlying mechanism and the association between UNC5B-AS1 and caspase-9.

Results: QRT-PCR results suggested that UNC5B-AS1 expression in PCa tissue samples was remarkably higher than in adjacent ones, with a statistically significant difference. Compared with patients with low expression of UNC5B-AS1, patients with highly-expressed UNC5B-AS1 had a higher incidence of distant metastasis and more advanced pathological stage. At the same time, proliferation and invasion, as well as migration ability of cells in sh-UNC5B-AS1 group, was conspicuously attenuated while cell apoptosis ability was conversely enhanced. Furthermore, qRT-PCR results revealed that caspase-9 and UNC5B-AS1 showed a negative correlation in gene expression level in PCa tissues. The results of the luciferase reporter gene experiment demonstrated that UNC5B-AS1 can be targeted by caspase-9 through their binding site. Additionally, cell recovery experiment indicated that UNC5B-AS1 and caspase-9 can be mutually regulated, which then together affect the malignant progression of PCa.

Conclusions: UNC5B-AS1 expression was found remarkably increased in both PCa tissues and cell lines, which was remarkably associated with pathological stage and incidence of distant metastasis of PCa patients. In addition, UNC5B-AS1 was able to accelerate the malignant progression of PCa by modulating caspase-9 expression.