Downregulation of lncRNA ZEB1-AS1 Represses Cell Proliferation, Migration, and Invasion Through Mediating PI3K/AKT/mTOR Signaling by miR-342-3p/CUL4B Axis in Prostate Cancer.

ABSTRACT

Background: Prostate cancer (PCa) is the second most common cancer among men, threatening men's health and life. Long noncoding RNA Zinc-finger E-box binding homeobox 1 antisense gene 1 (ZEB1-AS1) and Cullin 4B (CUL4B) were reported to be connected with the tumorigenesis of PCa. However, it is unclear whether ZEB1-AS1 regulates the expression of CUL4B in PCa. Materials and Methods: The levels of ZEB1-AS1 and CUL4B in PCa tissues and cells were evaluated by quantitative real-time polymerase chain reaction. Protein levels of CUL4B, p21, CyclinD1, matrix metalloprotease 9 (MMP9), E-cadherin, phosphorylated-phosphatidylinositol 3 kinase (p-PI3K), PI3K phosphorylated protein kinase B (p-AKT), AKT, p-mTOR and mammalian target of rapamycin (mTOR) in PCa tissues or cells were assessed by Western blot analysis. The proliferation, migration, and invasion abilities of PCa cells were determined with 3-(4, 5-dimethylthiazol-2-YI)-2,5-diphenyltetrazolium bromide (MTT) or transwell assay. The interaction between ZEB1-AS1 or CUL4B and microRNA-342-3p (miR-342-3p) was predicted using starBase v2.0 database and confirmed by the dual-luciferase reporter assay. Results: ZEB1-AS1 and CUL4B were upregulated and miR-342-3p was downregulated in PCa tissues and cells. Both ZEB1-AS1 and CUL4B inhibition constrained proliferation, migration, and invasion of PCa cells. Moreover, the elevation of CUL4B reversed the effects of ZEB1-AS1 silencing on the proliferation, migration, and invasion of PCa cells. Importantly, ZEB1-AS1 modulated CUL4B expression by sponging miR-342-3p in PCa cells. Besides, ZEB1-AS1 mediated PI3K/AKT/mTOR signal pathway by miR-342-3p/CUL4B axis in PCa cells. Conclusion: ZEB1-AS1 modulated PCa progression through mediating PI3K/AKT/mTOR signaling by miR-342-3p/CUL4B axis, providing a possible strategy for the treatment of PCa.