Long non-coding DANCR targets miR-185-5p to upregulate LIM and SH3 protein 1 promoting prostate cancer via the FAK/PI3K/AKT/GSK3β/snail pathway

Background: Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) acts as an oncogene in different cancers, although its roles in prostate Cancer are not fully reported. We aimed to explore its mechanism in facilitating the malignancy of prostate Cancer.

Methods: The expression of DANCR, MicroRNA (miR)-185-5p and LIM and SH3 protein 1 (LASP1) in 40 pairs of prostate Cancer tissues and normal tissues, five prostate Cancer cell lines and one epithelial cell line was assessed by a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry, respectively. In transfected PC3 and C4-2 cells, cell proliferation, migration, invasion, cell cycle distribution and epithelial-mesenchymal transition (EMT) protein expression were tested via cell counting kit-8, wound healing, transwell, flow cytometry and western blot assays, respectively. The interactions between DANCR, miR-185-5p and LASP1 were verified by a dual-luciferase reporter assay. Rescue experiments were conducted to determine the roles of DANCR on the malignant properties of PC3 and C4-2 cells. The involvement of the signaling pathway was examined using a p-FAK inhibitor.

Results: DANCR and LASP1 expression was enhanced, whereas miR-185-5p expression was diminished in prostate Cancer tissues and cell lines. Knockdown of DANCR suppressed cell proliferation, migration, invasion, G1-S transition and expression of EMT proteins of the transfected PC3 and C4-2 cells. DANCR sponged miR-185-5p to upregulate LASP1 expression. DANCR-miR-185-5p-LASP1 axis activates the FAK/PI3K/Akt/GSK3β/Snail pathway to promote the malignant properties of PC3 and C4-2 cells.

Conclusions: These findings suggest that DANCR exerts oncogenic roles in prostate Cancer via the miR-185-5p/LASP1 axis activating the FAK/PI3K/Akt/GSK3β/Snail pathway. It can be a potential biomarker in the diagnosis and monitoring of prostate Cancer.